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Abstract
Background
The objective of this study was to investigate the frequency and characteristics of HLA-DR-/CD34- acute myeloid leukemia (AML) also known as acute promyelocytic leukemia (APL)-like AML
Methods
This study included 683 newly diagnosed patients with AML. After exclusion of 211 patients with recurrent genetic abnormalities, one with acute panmyelosis with myelofibrosis, two with myeloid leukemia associated with Down syndrome, and two devoid of metaphase cells, we classified the remaining 467 patients as follows: group 1, HLA-DR+/CD34+ (typical AML); group 2, HLA-DR+/CD34- or HLA-DR-/CD34+; group 3, APL-like AML.
Results
Group 1 comprised 294 patients, group 2 comprised 133, and group 3 comprised 40. Therefore, the frequency of APL-like AML among 683 unselected patients with AML was 5.9%. Group 3 patients had significantly higher leukocyte counts and bone marrow (BM) blast percentages, higher frequencies of normal karyotypes and NPM1 mutation, higher fractions of CD33-positive cells, higher concentrations of fibrin degradation products and D-dimers, lower frequencies of complex karyotypes, monosomal karyotypes and poor cytogenetic risk, lower fractions of CD13-positive cells, and lower fibrinogen concentrations, compared with group 1 patients. The values of the BM blast percentage, number of CD33-positive cells, and DIC score of the patients with APL-like AML were intermediate between those of the patients with typical AML and APL.
REFERENCES
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Fig. 1.
The distribution and frequency of cases with high bone marrow blasts, CD33-positive cells, and DIC score. Patients with APL-like AML (group 3) showed an intermediate feature between HLA-DR+/CD34+ (group 1) and true APL cases. The cutoff values for bone marrow blasts (76.0%) and CD33-positive cells (91.4%) were derived from values corresponding to the 75 percentile of patients with group 1. The cutoff value for DIC score (5) was based on the ISTH consensus proposal. The frequencies of BM blast ≥76.0% were 25.2% in group 1, 22.6% in group 2, 45.0% in group 3, and 69.1% in APL. The frequencies of CD33-positive cell ≥91.4% were 25.2% in group 1, 52.6% in group 2, 70.0% in group 3, and 96.3% in APL. The frequencies of ISTH DIC score ≥5 were 12.3% in group 1, 23.6% in group 2, 51.5% in group 3, and 70.4% in APL. All of these three variables (BM blast, CD33-positive cell, DIC score) were significant (each, P<0.001) by Chi-square test for trends.
Table 1.
Comparison of demographics, and clinicopathological features among the patient groups
| Group 1 (N=294) | Group 2 (N=133)† | Group 3 (N=40)‡ | APL (N=55) | P value | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 v 2 | 1 v 3 | 2 v 3 | 1 v APL | 2 v APL | 3 v APL | |||||
| Age, yr (range) | 56.5 (3-83) | 57 (0.1–90) | 59 (1–80) | 46 (7–74) | 0.317 | 0.767 | 0.808 | <0.0001 | 0.002 | 0.012 |
| Pediatric age (%) | 16 (5.4) | 11 (8.3) | 3 (7.5) | 2 (3.6) | 0.369 | 0.870 | 0.862 | 0.823 | 0.410 | 0.713 |
| Male sex (%) | 184 (62.6) | 72 (54.1) | 23 (57.5) | 22 (40.0) | 0.123 | 0.654 | 0.846 | 0.003 | 0.109 | 0.139 |
| WBC count, ×109/L (range) | 4.45 (0.5–455) | 13.2 (0.3–363.4) | 17.8 (1.4–144.3) | 5.1 (0.4–196.4) | 0.0001 | 0.0001 | 0.192 | 0.842 | 0.032 | 0.005 |
| Hemoglobin level, g/dL (range) | 8.8 (3.3–17.3) | 8.5 (3.7–13.0) | 8.75 (4.1–13.5) | 8.5 (4.6–11.9) | 0.479 | 0.835 | 0.595 | 0.188 | 0.429 | 0.327 |
| Platelet count, ×109/L (range) | 55.5 (3–1019) | 75 (4–796) | 58.5 (11–312) | 40 (7–135) | 0.028 | 0.477 | 0.685 | 0.023 | 0.0003 | 0.035 |
| BM blast, % (range) | 49.6 (6.6–96.2) | 53.2 (3.0–93.2) | 73.1 (16.0–94.0) | 83.6 (25.6–96.6) | 0.573 | 0.0003 | 0.0007 | <0.0001 | <0.0001 | 0.012 |
| FAB subtype (%) | <0.0001 | 0.174 | 0.008 | |||||||
| M0 | 19 (6.5) | 3 (2.3) | 2 (5.0) | |||||||
| M1 | 89 (30.3) | 29 (21.8) | 20 (50.0) | |||||||
| M2 | 146 (49.7) | 43 (32.3) | 12 (30.0) | |||||||
| M4 | 17 (5.8) | 32 (24.1) | 3 (7.5) | |||||||
| M5 | 3 (1.0) | 14 (10.5) | 1 (2.5) | |||||||
| M6 | 13 (4.4) | 7 (5.3) | 2 (5.0) | |||||||
| M7 | 7 (2.4) | 5 (3.8) | 0 | |||||||
| WHO subtype (%) | 0.0003 | 0.009 | <0.0001 | |||||||
| AML, NOS | 145 (49.3) | 48 (36.1) | 30 (75.0) | |||||||
| AML with MRC | 127 (43.2) | 83 (62.4) | 8 (20.0) | |||||||
| tAML | 22 (7.5) | 2 (1.5) | 2 (5.0) | |||||||
| Cytogenetics (%)§ | ||||||||||
| NK | 102/289 (35.3) | 63/130 (48.5) | 26/37 (70.3) | 0.015 | 0.0001 | 0.031 | ||||
| Complex | 71/289 (24.6) | 17/130 (13.1) | 4/37 (10.8) | 0.011 | 0.094 | 0.932 | ||||
| MK | 63/289 (21.8) | 14/130 (10.8) | 3/37 (8.1) | 0.011 | 0.084 | 0.870 | ||||
| Cytogenetic risk | 0.0006 | 0.008 | 0.517 | |||||||
| Poor | 98/289 (33.9) | 22/130 (16.9) | 4/37 (10.8) | |||||||
| Intermediate | 191/289 (66.1) | 108/130 (83.1) | 33/37 (89.2) | |||||||
| Mutations (%) | ||||||||||
| FLT3-ITD | 44/291 (15.1) | 29/132 (22.0) | 9/39 (23.1) | 12 (21.8) | 0.112 | 0.299 | 0.942 | 0.300 | 0.864 | 0.915 |
| NPM1 | 13/274 (4.7) | 42/126 (33.3) | 28/37 (75.7) | <0.0001 | <0.0001 | <0.0001 | ||||
| CEBPAll | 17/179 (9.5) | 0/80 | 0/21 | 0.010 | 0.288 | NA | ||||
| MLL-PTD | 8/124 (6.5) | 6/66 (9.1) | 0/11 | 0.710 | 0.840 | 0.664 | ||||
§ We excluded eleven cases with suboptimal metaphase (<20 metaphase with no cytogenetic abnormalities) from the analysis;
ll Only biallelic CEBPA mutations were calculated. Abbreviations: APL, acute promyelocytic leukemia; v, versus; WBC, white blood cell; BM, bone marrow; FAB, French-American-British; NOS, not otherwise specified; MRC, myelodysplasia-related changes; tAML, therapy-related acute myeloid leukemia; NK, normal karyotype; MK, monosomal karyotype; ITD, internal tandem duplication; NA, not available; PTD, partial tandem duplication.
Table 2.
Comparison of immunophenotypic characteristics among the patient groups
| Group 1∗ (N=294) | Group 2 (N=133)† | Group 3 (N=40)‡ | APL (N=55) | P value | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 v 2 | 1 v 3 | 2 v 3 | 1 v APL | 2 v APL | 3 v APL | |||||
| CD117, N (%) | 283 (96.3) | 79 (59.4) | 31 (77.5) | 53 (96.4) | <0.0001 | <0.0001 | 0.058 | 0.726 | 0.0001 | 0.012 |
| CD33, N (%) | 277 (94.2) | 130 (97.7) | 39 (97.5) | 55 (100.0) | 0.177 | 0.625 | 0.610 | 0.137 | 0.629 | 0.872 |
| CD13, N (%) | 284 (96.6) | 120 (90.2) | 37 (92.5) | 55 (100.0) | 0.014 | 0.411 | 0.901 | 0.343 | 0.037 | 0.142 |
| CD33, % (range)§ | 76.65 (0.8–99.5) | 91.8 (5.3–99.5) 9 | 96.05 (23.2–99.6) | 98.6 (48.7–99.9) | <0.0001 | <0.0001 | 0.012 | <0.0001 | <0.0001 | 0.0001 |
| CD13, % (range)§ | 81.7 (1.8–99.6) | 69.7 (0.9–98.9) | 56.8 (3.6–97.9) | 93.5 (41.1–99.7) | <0.0001 | <0.0001 | 0.133 | <0.0001 | <0.0001 | <0.0001 |
| CD33%/CD13%, ratio (range) | 1.0 (0-50.7) | 1.2 (0.1–60.5) | 1.7 (0.3–26.3) | 1.0 (0.6–2.4) | <0.0001 | <0.0001 | 0.023 | <0.0001 | 0.009 | <0.0001 |
| CD65, N (%) | 118 (40.1) | 85 (63.9) | 14 (35.0) | 42 (76.4) | <0.0001 | 0.652 | 0.002 | <0.0001 | 0.137 | 0.0001 |
| CD15, N (%) | 158 (53.7) | 98 (73.7) | 18 (45.0) | 27 (49.1) | 0.0002 | 0.384 | 0.001 | 0.626 | 0.002 | 0.852 |
| CLEll | ||||||||||
| CD56, N (%) | 40 (13.6) | 23 (17.3) | 11 (27.5) | 8 (14.5) | 0.397 | 0.040 | 0.231 | 0.978 | 0.806 | 0.194 |
| CD2, N (%) | 20 (6.8) | 5 (3.8) | 1 (2.5) | 22 (40.0) | 0.309 | 0.481 | 0.912 | <0.0001 | <0.0001 | 0.0001 |
| CD7, N (%) | 73 (24.8) | 12 (9.0) | 1 (2.5) | 4 (7.3) | 0.0003 | 0.003 | 0.303 | 0.007 | 0.917 | 0.573 |
| TdT, N (%) | 15 (5.1) | 1 (0.8) | 0 | 0 | 0.055 | 0.292 | 0.523 | 0.177 | 0.648 | NA |
| Others, N (%) | 8 (2.7) | 6 (4.5) | 1 (2.5) | 0 | 0.504 | 0.660 | 0.914 | 0.455 | 0.252 | 0.872 |
§ The percentage (%) indicates the proportion of CD33 or CD13-positive cells among the total number of cells tested;
ll The distributions of cross-lineage antigen expression may overlap with each other. For example, the patient expressing both CD56 and CD7 was categorized as CD56 and CD7. Abbreviations: APL, acute promyelocytic leukemia; v, versus; N, number of a positive case; CLE, cross-lineage expression; NA, not available.
Table 3.
Comparison of concentration of markers for fibrin formation and fibrinolysis among the patient groups
| Group 1∗ | Group 2† | Group 3‡ | APL | P value | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| (N=294) | (N=133) | (N=40) | (N=55) | 1 v 2 | 1 v 3 | 2 v 3 | 1 v APL | 2 v APL | 3 v APL | |
| Fibrinogen (mg/dL)§ | 350 (54-845) | 367 (28–907) | 308 (52–771) | 123.5 (5–384) | 0.669 | 0.009 | 0.012 | <0.0001 | <0.0001 | <0.0001 |
| FDP (μg/mL)ll | 5.1 (0–87.6) | 6.3 (0–120.0) | 33.45 (4.2–102.9) | 47.95 (5.6–130.1) | 0.094 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | 0.011 |
| D-dimer (μg/mL FEU)¶ | 1.14 (0.06–39.50) | 1.765 (0.16–59.10) | 15.25 (0.27-321.0) | 18.95 (2.12–494.0) | 0.016 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | 0.534 |
| DIC score ≥5, N (%)∗∗ | 23 (12.3) | 21 (23.6) | 17 (51.5) | 38 (70.4) | 0.026 | <0.0001 | 0.006 | <0.0001 | <0.0001 | 0.123 |
§ Test results were available for 190 patients of group 1, 89 of group 2, 34 of group 3, and 54 of APL;
ll Test results were available for 167 patients of group 1, 83 of group 2, 30 of group 3, and 52 of APL;
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