The prognostic impact of different subsets of natural killer cells among Iraqi patients with AML

Обложка

Цитировать

Полный текст

Аннотация

Background: Acute myeloid leukemia (AML) is a diverse disease characterized by a wide range of genetic alterations and molecular abnormalities that influence clinical outcomes and provide prospective therapeutic targets. The immune evasion and active immune suppression by AML are due in part to the leukemia's inherent make-up as well as mechanisms acquired via subsequent mutation under selection pressure. Natural killer (NK) cells perform critical roles in the body's first-line innate defenses against viral infections, tumor progression, and metastatic dissemination. The constitutive production of effective, ready-to-use lytic machinery, as well as the quick release of interferon-gamma (IFN-α) and tumor necrosis factor-alfa (TNF-α) upon cell activation, allow for early intervention by NK cells, resulting in target cell destruction and the induction of an inflammatory response. NK cells depend on the balance of both inhibitory and activating receptor signals to select which target cells will be attacked or tolerated

Patients and methods: Thirty AML patient at diagnosis enrolled in this study from Baghdad teaching hospital, follow up these patients after 14 days of treatment and get result of remission after 30 days of treatment, twenty healthy looking persons considered as control subject. The technique used to detection of NK cells and their subsets was Flowcytometry.

Result: Decrease number of total NK in AML patients. The NK cells subset appear in patient was CD56bright CD16dim.

Conclusion: NK cells and their subset can be used as diagnostic and prognostic biomarker for AML patients.

Полный текст

Introduction:

Acute myeloid leukemia (AML) is a clonal disorder characterized by the proliferation and the accumulation of myeloid precursors in the bone marrow (BM) as result of recurrent genetic, epigenetic, and metabolic abnormalities that show aberrant differentiation patterns leading to hematopoietic impairment 24.

AML is a very variable illness that can manifest as "a de novo or secondary disease" (therapy-related or post-antecedent hematologic condition). The incidence of onset rises with age, and age is also linked to a larger frequency of high-risk cytogenetic and molecular abnormalities35.

Although AML accounts for only about 1% of all cancers with an incidence of 4 per 100,000 a year, it is the most common acute leukemia in adults 19,8,15.  AML is often associated with elderly persons and is uncommon before the age of 45, while it can occur at any age. The typical age upon diagnosis is 68 years, with most individuals diagnosed between the ages of 65 and 74 years (30 and predominant in male more than female 18,7.

The immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying tumor cells or inhibiting their overgrowth but also induce tumor progression either by selecting for tumor cells that able to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor overgrowth 11,26.

Natural Killer cells ( NK ) are large granular lymphocytes arising from the lymphoid origin which are deemed as the third largest population of lymphocytes following T and B cells include (10-15%) of all peripheral blood lymphocytes involved in defense against certain virus-infected and malignant cells 33. In contrast to T cells, NK cells elicit rapid anti-tumor responses based on signals from activating and inhibitory cell surface receptors (22. They also lyse target cells via antibody-dependent cellular cytotoxicity (ADCC), a critical mode of action of several therapeutic antibodies used to treat cancer 5. Without prior sensitization, NK cells are innate lymphoid cells that contribute to the immune system's first-line defense against infections and malignant cells 32,10. NK cells are divided into two categories based on surface expression levels of CD56 and CD16 as determined by immunofluorescence intensity. The standard CD56dimCD16bright, inhibitory and/or activating receptors 6.  In general, the major subpopulations of NK cells are CD56bright CD16−/+ (5-10% of NK cells) and CD56dim CD16+ NK cells (90-95% of NK cells), is a potent producer of immunoregulatory cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α/β and interleukin IL-10 16,17(6,34). NK cells rely on the balance of both inhibitory and activating receptor signals to determine which target cells will be attacked or tolerated 25,14.

Patients and methods:

Patients: Thirty patients diagnosed as AML divided to 19 male and 11 female and follow-up at day 14 at treatment and at day 30 after treatment were collected from Baghdad Medical City, from February 2021 to November 2021. Twenty healthy looking persons match age and sex with patient considered as control subject.

In this study, the inclusion criteria were that patients newly diagnosed with any type of acute myeloid leukemia except AML-M3. Bone marrow aspirate sample available for immunophenotyping study with multicolor FC, of any sex, age 18 - 65 years. The treatment 7+3 regimen.

Exclusion criteria were age under 18 years, AML -M3 patients, another treatment protocol.

The patients’ peripheral blood (PB) and bone marrow aspirate (BMA) samples were received as fresh as possible and for each patient the following analysis were performed in diagnostic settings: full blood count, peripheral blood film and BMA smear morphology with SBB staining if morphology of blast cells was not showing clear myeloid differentiation, BMA multicolor FC testing for Using multicolor FC to evaluate the expression of CD7, CD11c, CD13, CD14, CD19, CD33, CD34, CD45, CD64, CD117 and MPO in adult patients with morphologically, cytogenetic analysis and genetic mutation ( NPM-1 and FLT-3 ), newly diagnosed AML

Study design: This is a cohort study that was performed in diagnostic laboratory settings

 

Collection of blood samples from each patient and healthy-looking patients, 5 ml of vein puncture blood sample was taken by using a syringe, dispensed in 2 tubes containing EDTA each with 1.5 ml, one for complete blood count and flow cytometry analysis.

 

Detection of NK cells, their subsets by flowcytometry.

In present study 8-collor Flow cytometry BD FACSCANTO II instrument was used to detect Immunophenotyping NK cells and their subsets in patients with AML and control subject.

The Surface receptors used for detection NK cells is (CD45 conjugated Violate 500 (V500), CD3 conjugated Violate 450 (V450), CD56 conjugated allophycocyanin (APC), CD16 conjugated ( PerCP - Cyanines 5.5), The NK cells immunophenotype  is ( CD45+,CD3-,CD56+,CD16+).All antibodies were products either (Elabscience/ China) and Santa Cruz biotechnology/UK)

Sample processing for BD FACSCANTO II flow cytometer: Using the following techniques with the principle of Stain–Lyse–Wash.

Preparation of reagents

Reagents were prepared according to the manufacturer’s instructions as follow:  Red Blood Cell (RBC) Lysis Buffer: Prepared by Dilute 1ml of 10X RBC Lysis Buffer with 9ml distilled water to form 1x working concentration. Then warmed to room temperature prior to use.

 Flow cytometry staining of whole blood procedure:

 five μl of fluorochrome conjugated antibodies (CD45-V500, CD3-V450, CD56-APC, CD16- PerCP - Cyanines 5.5) were added to 100μl of anti-coagulated blood. Another tube had 100μl of whole blood used as unstained control. Tubes were incubated in the dark for 15 minutes at room temperature. Next, 2ml of 1X RBC lysis solution was added to both tubes (stained and unstained) then incubated in the dark for 10 minutes at room temperature. The tubes were centrifuged for 5 minutes at 2300 rpm, discarding the supernatant. Tubes were washed with 2ml of cell wash solution via centrifugation for 5 minutes at 2300rpm, discarding the supernatant. Pellets were resuspended in 0.5mL of 1X cell fix buffer. Then both tubes were acquired on flow cytometric analysis FACS Canto II (BD BIOSCENCES) and analyzed with DIVA software version 2016. At least 100,000 events were analyzed for each sample.

Gating:

Gating strategy used to identify NK cells and their subsets and receptors; The serial gating used in this study involved in the first plot gating on viable cells using forward scatter (FSC) versus side scatter (SSC) plot lymphocytes were selected by CD45 versus side scatter (SSC) Then Gating on CD56 verses CD3. NK cells were identified by the expression of CD56 and CD16 and the absence of CD3. CD56 + CD16 + cells were select NK cells subset according to the florescent emission either CD56 Bright CD16 dim (Cytokines producers) and CD56 dim CD16 bright (Cytotoxic NK cells) figures (1), (2), (3), (4), (5) and (6).

Figure 1: Flow cytometry analysis of AML patient at zero day. a)  dot plot to of unstained cells b) dot plot to choose singlets cells c) dot plot to identify CD45+  d) dot plot to identify CD3- CD56+ population e) dot plot to identify CD56+CD 16+  ( NK cells ) as well as detection of CD56bright CD16dim (p4) and  CD56dim CD16bright  (p3)

Figure 2: Hierarchy analysis data from cells stained with Anti-CD45, Anti-CD3, Anti-CD56, Anti-CD16.

Figure 3: Flow cytometry analysis of AML patient after 14 days treatment. a)  dot plot to of unstained cells b) dot plot to choose singlets cells c) dot plot to identify CD45+  d) dot plot to identify CD3- CD56+ population e) dot plot to identify CD56+CD 16+  ( NK cells ) as well as detection of CD56bright CD16dim (p4) and  CD56dim CD16bright  (p1)

Figure 4: Hierarchy analysis data from cells stained with Anti-CD45, Anti-CD3, Anti-CD56, Anti-CD16.

f

eb

 

Figure 5: Flow cytometry analysis of control subject. a)  dot plot to of unstained cells b) dot plot to choose singlets cells c) dot plot to identify CD45+  d) dot plot to identify CD3- CD56+ population e) dot plot to identify CD56+CD 16+  ( NK cells ) as well as detection of CD56bright CD16dim (p4) and  CD56dim CD16bright  (p1) .

 

Figure 6: Hierarchy analysis data from cells stained with Anti-CD45, Anti-CD3, Anti-CD56, Anti-CD16.

Statistical analysis:

Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 23.0.0. Analytic statistics was carried out using t-test with p-value of ˂0.05 was considered significant. Descriptive statistics was presented into tables, bar charts, stem and leaf plots, scatter plots and trend-line mainly in the form of range, mean and standard deviation.

Result:

General characteristics of the studied groups.

The patients enrolled in this study 30 patients diagnosed with AML at day zero of therapy and 24 out of 30 patients were followed up at day 14 after therapy,19 males and 11 females with male: female ratio 1.72:1, table (1), 6 patients out of 30 were deceased. 20 healthy looking persons considered as a control subjects.

Mean age of patients with AML was 40.2±15.2 years and range from 18 - 65 years, while the mean for the control subjects was 41.1±13.3 years and range from 24 - 64 years, table (2) and figure (7).

Table 1: Sex distribution of patients with AML:

Sex group

Patients

(n=30)

Control subjects

(n=20)

No.

%

No.

%

Males

19

63

13

65

Females

11

27

7

25

Male: Female

1.72:1

1.86:1

 

Table 2: Age distribution of patients with AML:

Age group

(years)

Patients

(n=30)

Control subjects

(n=20)

No.

%

No.

%

16-25

8

26.6

2

10

26-35

4

13.3

6

30

36-45

7

23.4

6

30

46-55

5

16.7

2

10

56-65

6

20

4

20

Range

18-65

24-64

Mean ± SD

40.2 ± 15.2

41.1 ± 13.3

 

 

 

Figure 7: Age distribution of patients with AML at diagnosis and at 14 days after treatment.

Hematological abnormalities in AML patients' group

In this study, there were two or more abnormalities including anemia, thrombocytopenia, leucopenia or leukocytosis, neutropenia and presence of blast cells with newly diagnosed patients with AML. The results for the abnormalities of complete blood count (CBC) and presence of blast cells in peripheral blood film in patients with AML are presented in table (3).

 

 

 

Table 3: Abnormalities of CBC and presence of blast cells in peripheral blood film in patients with AML:

Parameter/ Patients

(n=30)

At diagnosis

(n=30)

At day 14 after treatment

(n=24)

No.

%

No.

%

Anemia

Present

27

90

22

91.7

Absent

3

10

2

8.3

Platelet count

(X109/l)

≥ 100

6

20

2

8.3

< 100

24

80

22

91.7

WBC count

(X109/l)

> 10.0

18

60

1

4.2

4.0-10.0

4

13.3

2

8.3

<4.0

8

26.7

21

87.5

Neutrophils (%)

>70

0

0

15

62.5

40-70

5

16.7

4

16.6

<40

25

83.3

5

20.9

Monocytes (%)

3 - 12

10

33.3

6

25

<3.0

15

50

11

45.8

>12.0

5

16.7

7

29.2

Lymphocytes (%)

<20

23

76.7

20

83.3

20-40

0

0

0

0

>40

7

23.3

4

16.7

Eosinophils (%)

1-5

8

26.7

6

25

<1.0

22

73.3

18

75

Basophils (%)

0.1-1

2

6.7

16

66.7

<0.1

28

93.3

8

33.3

Immature/ Blast cells

Present

30

100

7

29.2

Absent

0

0

17

70.8

Alive/ Deceased

Alive

30

100

24

80

Deceased

0

0

6

20

 

Hematological remission with patient of AML:

Hematological remission is defined as absence of clinical evidence of leukemia with bone marrow blast cells <5%, absence of Auer rods, neutrophil count ≥1*109/l, and platelet count ≥ 100*109/l 4. 15 (62.5%) out of 24 of patient with AML at day 30 after treatment were in remission, and 9 (37.5%) out of 24 patients were not in remission, table (4).

Table 4: Hematological remission of patients with AML at day 30 after treatment:

Patients (n=24)

No.

%

Remission

15

62.5

No remission

9

37.5

 

 

Presence of NK cells and their subsets.

According to data presented in table (5), there was a statistically significant difference in the proportion of cells in the CD45+ CD3- CD56+ CD16+ (Natural killer cells) in patients with AML at diagnosis and at day 14 after treatment (mean±SD) (2.82±2.96, 1.308±1.928) respectively, with p-value (0.04). While there was no statistically significant difference in patients with AML at diagnosis and at day14 after treatment, and control subject p-value (0.134, 0.56) .

For cytokine-producer NK cells (CD45+ CD3- CD56bright CD16dim) there were no statistically significant difference in patients with AML at diagnosis and day 14 after treatment (5.08 ± 5.06, 6.56 ± 1.928) respectively, with p-value (0.39). On the contrary, there were a statistically significant difference between patients with AML at diagnosis (5.08±5.06), and AML at day 14 after treatment (6.56±7.63) compared with control subjects (0.03±0.09), p-value (0.001, 0.001).

For cytotoxic NK cells (CD45+ CD3- CD56dim CD16bright) there were statistically significant difference in patients with AML at diagnosis (7.55±7.29) and AML at day 14 after treatment (3.64±2.97) compared with control subject (18.8 ±17.6) p-value (0.017,0.03,0.001) respectively.

 

Table 5: Comparison of presence of NK cells and their subsets in AML patients at diagnosis and after 14 days therapy in comparison to control subjects:

CD expression (%)

Range (Mean ± SD)

Patients

Control subjects (n=20)

p-value compare to

At diagnosis

(n=30)

At day 14

(n=24)

at diagnosis and at 14 days after treatment

at diagnosis and control subjects.

at 14 days after treatment and control subjects.

CD45+ CD3- CD56+ CD16+

0.1 – 12.5

(2.82±2.96)

0.3 – 9.6 (1.308±1.928)

0.3 – 5.6

(1.66±2.03)

0.04

0.134

0.56

CD45+ CD3- CD56bright CD16dim

0 – 20.9

(5.08 ± 5.06)

0 – 25.1

(6.56 ± 7.63)

0 – 0.3

(0.03 ± 0.09)

0.39

<0.001

<0.001

CD45+ CD3- CD56dim CD16bright

0.7 – 34.9

(7.55 ± 7.29)

0.4 – 9.8

(3.64 ± 2.97)

1.3 – 48.7

(18.8 ±17.6)

0.017

0.03

<0.001

significant p value <0.05

highly significant p- value <0.01

         

Presence of NK cells and their subsets in patients with AML in relation to mortality.

According to the data presented in table (6), in relation to mortality, there were no statistically significant differences in the proportion of cells in the total NK cells, cytokine producer NK cells, cytotoxic NK cells.

 

Table 6: Comparison of presence of NK cells and their subsets in patients with AML, in relation to mortality:

CD expression (%) at diagnosis

Range (Mean ± SD)

Alive

(n=24)

Deceased

(n=6)

p-value

CD45+ CD3- CD56+ CD16+

0 - 9.9

(2.39±2.53)

0.6 - 12.5

(4.4±4.16)

0.128

 CD56bright CD16dim

0 - 20.9

(5.3±4.44)

0.5 - 7.7

(4.2±3.81)

0.648

 CD56dim CD16bright

0.7- 17.4

(6.72±5.19)

1.7 - 34.9

(10.86±12.96)

0.219

significant p value <0.05

highly significant p- value <0.01

 

Presence of NK cells and their subsets in patients with AML in relation to remission at 30 days after treatment.

According to the data presented in table (7), In regarding to remission at 30 days after treatment, there was no statistically significant difference in the proportion of cells in the Total NK cells, cytokine producer NK cells, cytotoxic NK cells.

Table 7: Comparison of presence of NK cells and their subsets at diagnosis in patients with AML, in relation to remission at 30 days after treatment:

CD expression (%) at diagnosis

Range (Mean ± SD)

Remission

(n=15)

No remission

(n=9)

p-value

CD45+ CD3- CD56+ CD16+

0.1-9.9

(2.07±2.62)

0.2 - 7.0

(2.7 ±2.39)

0.598

CD56bright CD16dim

0 - 8.8

(4.16±2.72)

1.0 - 20.9

(7.21 ±7.9 )

0.173

 CD56dim CD16bright

0 - 14.3

(7.20 ± 5.34)

0.8 - 17.4

(5.92 ± 5.13)

0.569

significant p value <0.05

highly significant p- value <0.01

 

 

Discussion:

Acute myeloid leukemia is a bone marrow malignancy defined by the clonal proliferation and differentiation arrest of myeloid progenitor cells. In the United States (US), the incidence of AML is 4.3 per 100,000 per year 27. In Iraq Abdulridha and colleges studied 3102 of leukemia patients in the Iraqi Center for Hematology in the City of Medicine in Baghdad between January 2018 and December 2019, AML was 37% of total leukemia in 2018 while in 2019 AML was 40.8 % of total leukemia1

AML may affect people of all ages, from infants to the elderly 13,2. In the United States, the median age of AML diagnosis ranged from 62 to 68 years 31. Similar variations were seen in Europe and Canada 28,29. In Saudi Arabia, the median age at AML diagnosis seems to be lower than that reported for the United States and Europe, despite the fact that there is minimal data to support this notion. The current research, which included 30 patients with AML at the time of diagnosis and followed up 24 of those patients after 14 days of treatment, found that the mean age of patients with AML was (40.2±15.2 years, ranging from 18 to 65 years according to the exclusion criteria.

The AML patients in this study was 19 males and 11 females with male: female ratio 1.72:1. This result agrees with Juliusson and colleges as with most leukemia, AML is a more common hematological malignancy in males than in females 13.

The present research examines the overall number of NK cells and their subsets, in AML patients.

According to this study showed significant differences in proportion of NK cells between patients with AML at diagnosis and at day 14 after treatment (p-value = 0.04), while there were no significant differences between patients with AML at diagnosis, at day 14 after treatment, and control subjects (p-value 0.134, 0.56)

For cytokine-producer NK cells (CD56bright CD16dim), there was no statistically significant difference in patients with AML at diagnosis and day 14 after treatment p-value (0.39). On the contrary, there was a statistically significant difference between patients with AML at diagnosis and AML at day 14 after treatment with control subjects, p-value (0.001, 0.001), respectively. For cytotoxic NK cells (CD56dim CD16bright), there was statistically significant difference in patients with AML at diagnosis, AML at day 14 after treatment with control subject p-value (0.017, 0.03, 0.001), respectively.

Several research reports reported today relate impaired NK cell function with alterations in NK cell subset makeup, phenotype, and the capacity to create a completely functioning immunological junction 28. Natural killer cell deficiency (NKD) is a primary immunodeficiency in which CD56+CD3 natural killer (NK) cells that mediate cytotoxicity against malignancies are defective. The majority of cases are viral infections and cancers that keep coming back in children and teens 20.

Leukemia cells in AML may evade NK cell-mediated detection due to NK cell abnormalities, immunosuppressive features of AML cells, or interactions between NK cells and other immune cells that facilitate immune evasion 17. On the basis of surface expression levels of CD56 and CD16, as determined by the intensity of immunofluorescence, they may be divided into two categories 36. The classical CD56dimCD16bright NK cell subset constitutes about 90% of the overall population in peripheral blood and displays potent cytolytic activity by producing cytotoxic granules containing perforin and granzymes. CD56brightCD16dim NK cells are a prolific generator of immunoregulatory cytokines, including as interferon (IFN)-γ, tumor necrosis factor (TNF) α/β , and interleukin (IL-10) 6. Rey et al. (2017) found that in both AML patients, the immature NK cell population was lost selectively. This suggests that NK cell maturation is messed up in myeloid malignancies. This loss of primitive NK cells is accompanied by an increased percentage of phenotypically more CD56brightCD16negative/dim NK cells in the peripheral blood of AML patients 23 . But Aggarwal et al. (2016) found that the number of mature NK cells (CD56dimCD16bright) was lower in AML. NK cells from AML patients have defective cytolytic activities 3. With activating and inhibitory receptors, the function of NK cells is either inhibitory or activating depending on the balance between activating and inhibitory receptors on NK cells 16. For activating and inhibitory receptors, the function of NK cells can be either inhibitory or activating depending on the balance between activating and inhibitory receptors on NK cells.

In relation to mortality, there are no statistically significant differences in the proportion of cells in the total NK cells, their subsets, and inhibitory and activation receptors among AML at diagnosis and AML at day 14 after treatment. AML is a disease of older people, with a median starting age of 68 – 72 years. NK cell activity may not be a factor in AML morbidity 12. Song et al. (2018) found that older age is consistently related to worse survival and increased treatment-associated morbidity 31. Both tumor biology and age-related patient factors that reduce treatment tolerance are responsible for the poor prognosis of AML in older individuals 21.

According to the data reported in table (9) There is no statistically significant difference in the number of total NK cells and their subsets among AML patients at diagnosis and those in remission at 14 days and 30 days following therapy. In remission, we cannot consider the subsets and receptors of NK cells to be an indication of prognosis due to alterations in NK cell-activating receptors and their ligands in malignancies, which is one of the most prevalent problems that may lead to a diminished treatment response and tumor relapse 9.

Conclusion;

The observations of the present study were that total NK cells decreased in AML patients, (CD56bright CD16dim) elevated vs. (CD56 dim CD16 bright) NK cell subset, so NK cells and their subsets can be used as diagnostic and prognostic biomarkers for AML patients.

×

Об авторах

Baan Mtashar

The National Center of Hematology, Al-Mustansiriyah University, Baghdad, Iraq

Автор, ответственный за переписку.
Email: muhammedkareem51@gmail.com
ORCID iD: 0000-0003-0402-5216
Ирак

Zainab Ashoor

Department of Microbiology, College of Medicine, Almustansiriyah university, Baghdad, Iraq.

Email: zainab.fadhil@uomustansiriyah.edu.iq
ORCID iD: 0000-0003-0416-438X

Zeyad Shabeb

The National Center of Hematology, Al-Mustansiriyah University, Baghdad, Iraq

Email: dr.ziadahmed@gmail.com
ORCID iD: 0000-0003-4733-3382
Ирак

Bassam Matti

Bone Marrow Transplant Center, Medical City, Baghdad, Iraq

Email: bassam_francis@yahoo.com
Ирак

Список литературы

  1. Abdulridha RH, Jawad NK, Numan AT. Prevalence and risk of leukemia reported cases, observational descriptive statistic from Iraqi center for hematology in Baghdad province. Indian J Forensic Med Toxicol. 2021;15(1):2428-2433. doi: 10.37506/ijfmt.v15i1.13765
  2. Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nat 2018 5597714. 2018;559(7714):400-404. doi: 10.1038/s41586-018-0317-6
  3. Aggarwal N, Swerdlow SH, TenEyck SP, Boyiadzis M, Felgar RE. Natural killer cell (NK) subsets and NK-like T-cell populations in acute myeloid leukemias and myelodysplastic syndromes. Cytom Part B Clin Cytom. 2016;90(4):349-357. doi: 10.1002/CYTO.B.21349
  4. Bain BJ. Leukaemia Diagnosis.; 2010. doi: 10.1002/9780470988374
  5. Carlsten M, Järås M. Natural Killer Cells in Myeloid Malignancies: Immune Surveillance, NK Cell Dysfunction, and Pharmacological Opportunities to Bolster the Endogenous NK Cells. Front Immunol. 2019;10(October):1-18. doi: 10.3389/fimmu.2019.02357
  6. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633-640. doi: 10.1016/S1471-4906(01)02060-9
  7. De-Morgan A, Meggendorfer M, Haferlach C, Shlush L. Male predominance in AML is associated with specific preleukemic mutations. 35(3):867-870. Accessed October 10, 2021. https://www.nature.com/articles/s41375-020-0935-5
  8. Döhner H, Weisdorf DJ BC. [Acute myeloid leukemia]. N Engl J Med. 2015;373 Supp12:1136-1152. doi: 10.1056/NEJMra1406184
  9. Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol 2016 179. 2016;17(9):1025-1036. doi: 10.1038/ni.3518
  10. Hallner A, Bernson E, Hussein BA, et al. The HLA-B 221 dimorphism impacts on NK cell education and clinical outcome of immunotherapy in acute myeloid leukemia. Blood. 2019;133(13):1479-1488. doi: 10.1182/blood-2018-09-874990
  11. Hoffman R, Benz EJ, Silberstein LE, et al. Hematology: Basic Principles and Practice. Hematol Basic Princ Pract. Published online August 15, 2017:1-2374. doi: 10.1016/C2013-0-23355-9
  12. Institute N cancer (NIH). Cancer Statistics Review, Previous Version - SEER Cancer Statistics Review. Published online 2016. Accessed June 24, 2022. https://seer.cancer.gov/archive/csr/1975_2009_pops09/
  13. Juliusson G, Lehmann S, Lazarevic V. Epidemiology and Etiology of AML. Hematol Malig. Published online 2021:1-22. doi: 10.1007/978-3-030-72676-8_1/TABLES/1
  14. Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 2008 95. 2008;9(5):495-502. doi: 10.1038/ni1581
  15. Li K, Chen L, Zhang H, et al. High expression of COMMD7 is an adverse prognostic factor in acute myeloid leukemia. Aging (Albany NY). 2021;13(8):11988. doi: 10.18632/AGING.202901
  16. Lichtenegger FS, Lorenz R, Gellhaus K, Hiddemann W, Beck B, Subklewe M. Impaired NK cells and increased T regulatory cell numbers during cytotoxic maintenance therapy in AML. Leuk Res. 2014;38(8):964-969. doi: 10.1016/J.LEUKRES.2014.05.014
  17. Lion E, Willemen Y, Berneman ZN, Van Tendeloo VFI, Smits ELJ. Natural killer cell immune escape in acute myeloid leukemia. Leuk 2012 269. 2012;26(9):2019-2026. doi: 10.1038/leu.2012.87
  18. Maleki Behzad M, Abbasi M, Oliaei I, Ghorbani Gholiabad S, Rafieemehr H. Effects of Lifestyle and Environmental Factors on the Risk of Acute Myeloid Leukemia: Result of a Hospital-based Case-Control Study. J Res Health Sci. 2021;21(3). doi: 10.34172/JRHS.V0I0.6842
  19. Miller KD, Goding Sauer A, Ortiz AP, et al. Cancer Statistics for Hispanics/Latinos, 2018. CA Cancer J Clin. 2018;68(6):425-445. doi: 10.3322/caac.21494
  20. Moon WY, Powis SJ. Does Natural Killer Cell Deficiency (NKD) Increase the Risk of Cancer? NKD May Increase the Risk of Some Virus Induced Cancer. Front Immunol. 2019;10:1703. doi: 10.3389/FIMMU.2019.01703/BIBTEX
  21. Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97(12):1916-1924. doi: 10.3324/HAEMATOL.2012.066100
  22. Punt J, Stranford SA, Jones PP, Owen JA. Kuby Immunology.; 2019.
  23. Rey J, Fauriat C, Kochbati E, et al. Kinetics of cytotoxic lymphocytes reconstitution after induction chemotherapy in elderly AML patients reveals progressive recovery of normal phenotypic and functional features in NK cells. Front Immunol. 2017;8(FEB):64. doi: 10.3389/FIMMU.2017.00064/BIBTEX
  24. Richard-Carpentier G, DiNardo CD. Single-agent and combination biologics in acute myeloid leukemia. Hematol Am Soc Hematol Educ Progr. 2019;2019(1):548. doi: 10.1182/HEMATOLOGY.2019000059
  25. Samaridis J, Cella M, Allen RL, George’ S, O’callaghan C. Cutting Edge: Human Myelomonocytic Cells Express an Inhibitory Receptor for Classical and Nonclassical MHC Class I Molecules 1. Artic J Immunol. Published online 1998. Accessed May 4, 2022. https://www.researchgate.net/publication/237718010
  26. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion. Science (80- ). 2011;331(6024):1565-1570. doi: 10.1126/science.1203486
  27. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev. 2019;36:70-87. doi: 10.1016/J.BLRE.2019.04.005
  28. Shysh AC, Nguyen LT, Guo M, Vaska M, Naugler C, Rashid-Kolvear F. The incidence of acute myeloid leukemia in Calgary, Alberta, Canada: A retrospective cohort study. BMC Public Health. 2017;18(1):1-5. doi: 10.1186/s12889-017-4644-6
  29. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011 10511. 2011;105(11):1684-1692. doi: 10.1038/bjc.2011.450
  30. Solomon SR, Solh M, Jackson KC, et al. Real-world outcomes of unselected elderly acute myeloid leukemia patients referred to a leukemia/hematopoietic cell transplant program. Bone Marrow Transplant. 2020;55(1):189-198. doi: 10.1038/s41409-019-0675-1
  31. Song X, Peng Y, Wang X, et al. Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001–2013. Acta Haematol. 2018;139(2):115-127. doi: 10.1159/000486228
  32. Spits H, Artis D, Colonna M, et al. Innate lymphoid cells — a proposal for uniform nomenclature. Nat Rev Immunol 2013 132. 2013;13(2):145-149. doi: 10.1038/nri3365
  33. Taha M. TURKISH JOURNAL of ONCOLOGY Impairment of NK Cell Mediated Immune Surveillance Against Acute Myeloid Leukemia. J Oncol. 2022;37(2):214-236. doi: 10.5505/tjo.2022.2883
  34. Vivier E. What is natural in natural killer cells? Immunol Lett. 2006;107(1):1-7. doi: 10.1016/J.IMLET.2006.07.004
  35. Wiese M, Daver N. Unmet clinical needs and economic burden of disease in the treatment landscape of acute myeloid leukemia. Am J Manag Care. 2018;24(16):S347-S355.
  36. Xu J, Niu T. Natural killer cell-based immunotherapy for acute myeloid leukemia. J Hematol Oncol 2020 131. 2020;13(1):1-20. doi: 10.1186/S13045-020-00996-X
  37. Zhang W, Xie X, Mi H, et al. Abnormal populations and functions of natural killer cells in patients with myelodysplastic syndromes. Oncol Lett. 2018;15(4):5497-5504. doi: 10.3892/OL.2018.8062

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© Mtashar B., Ashoor Z., Shabeb Z., Matti B.,

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах