Comparison of clinical and molecular features among 3 distinct, circRNA expression–based clusters of younger adults with CN-AML
| Characteristic . | Cluster 1 (n = 115) . | Cluster 2 (n = 106) . | Cluster 3 (n = 144) . | P . |
|---|---|---|---|---|
| Age, y | .02 | |||
| Median | 50 | 43 | 46 | |
| Range | 19-59 | 17-59 | 18-59 | |
| Sex, n (%) | .06 | |||
| Male | 64 (56) | 61 (58) | 63 (44) | |
| Female | 51 (44) | 45 (42) | 81 (56) | |
| Race, n (%) | .75 | |||
| White | 102 (90) | 97 (92) | 125 (89) | |
| Nonwhite | 11 (10) | 8 (8) | 15 (11) | |
| Hemoglobin, g/dL | .17 | |||
| Median | 9.1 | 9.5 | 9.1 | |
| Range | 4.8-25.1 | 4.2-13.6 | 4.9-14.4 | |
| Platelet count, ×109/L | <.001 | |||
| Median | 76 | 51 | 47 | |
| Range | 9-433 | 8-445 | 8-270 | |
| WBC count, ×109/L | <.001 | |||
| Median | 42.8 | 15.3 | 29.0 | |
| Range | 1.9-308.8 | 0.8-223.8 | 0.6-475.0 | |
| Blood blasts, % | <.001 | |||
| Median | 44 | 64 | 68 | |
| Range | 0-95 | 0-97 | 0-97 | |
| BM blasts, % | .31 | |||
| Median | 70 | 65 | 70 | |
| Range | 18-96 | 19-95 | 21-95 | |
| Extramedullary involvement, n (%) | .005 | |||
| Present | 47 (41) | 23 (22) | 36 (26) | |
| Absent | 67 (59) | 80 (78) | 103 (74) | |
| ASXL1, n (%) | .12 | |||
| Mutated | 1 (1) | 6 (6) | 5 (4) | |
| Wild type | 108 (99) | 95 (94) | 131 (96) | |
| CEBPA, n (%) | <.001 | |||
| Double mutated | 1 (1) | 40 (39) | 13 (9) | |
| Wild type | 106 (99) | 63 (61) | 125 (91) | |
| DNMT3A, n (%) | <.001 | |||
| Mutated | 63 (57) | 23 (22) | 53 (39) | |
| Wild type | 48 (43) | 81 (78) | 84 (61) | |
| FLT3-ITD, n (%) | <.001 | |||
| Present | 36 (32) | 19 (19) | 82 (57) | |
| Absent | 77 (68) | 83 (81) | 61 (43) | |
| FLT3-TKD, n (%) | .02 | |||
| Present | 18 (16) | 5 (5) | 13 (9) | |
| Absent | 77 (68) | 83 (81) | 61 (43) | |
| IDH1, n (%) | .11 | |||
| Mutated | 6 (5) | 13 (13) | 8 (6) | |
| Wild type | 105 (95) | 91 (88) | 129 (94) | |
| IDH2, n (%) | .20 | |||
| Mutated | 7 (6) | 14 (13) | 13 (9) | |
| Wild type | 104 (94) | 90 (87) | 124 (91) | |
| NPM1, n (%) | <.001 | |||
| Mutated | 86 (80) | 26 (25) | 89 (66) | |
| Wild type | 22 (20) | 76 (75) | 45 (34) | |
| RUNX1, n (%) | .03 | |||
| Mutated | 4 (4) | 11 (11) | 4 (3) | |
| Wild type | 107 (96) | 93 (89) | 133 (97) | |
| SF1, n (%) | .52 | |||
| Mutated | 1 (1) | 1 (1) | 0 (0) | |
| Wild type | 110 (99) | 103 (99) | 137 (100) | |
| SF3A1, n (%) | 1.00 | |||
| Mutated | 0 (0) | 0 (0) | 1 (1) | |
| Wild type | 111 (100) | 104 (100) | 136 (99) | |
| SF3B1, n (%) | .32 | |||
| Mutated | 3 (3) | 5 (5) | 2 (1) | |
| Wild type | 108 (97) | 99 (95 | 135 (99) | |
| SRSF2, n (%) | .22 | |||
| Mutated | 2 (2) | 6 (6) | 3 (2) | |
| Wild type | 109 (98) | 97 (94) | 133 (98) | |
| TET2, n (%) | .61 | |||
| Mutated | 15 (14) | 12 (12) | 13 (9) | |
| Wild type | 96 (86) | 92 (88) | 124 (91) | |
| U2AF1, n (%) | .11 | |||
| Mutated | 3 (3) | 1 (1) | 0 (0) | |
| Wild type | 108 (97) | 103 (99) | 137 (100) | |
| U2AF2, n (%) | NA* | |||
| Mutated | 0 (0) | 0 (0) | 0 (0) | |
| Wild type | 111 (100) | 104 (100) | 137 (100) | |
| WT1, n (%) | .007 | |||
| Mutated | 6 (5) | 9 (9) | 24 (18) | |
| Wild type | 105 (95) | 95 (91) | 113 (82) | |
| ZRSR2, n (%) | .85 | |||
| Mutated | 4 (4) | 4 (4) | 7 (5) | |
| Wild type | 107 (96) | 100 (96) | 130 (95) | |
| ELN genetic group†, n (%) | <.001 | |||
| Favorable | 75 (69) | 65 (65) | 59 (45) | |
| Intermediate | 20 (18) | 17 (17) | 51 (39) | |
| Adverse | 14 (13) | 18 (18) | 20 (15) | |
| NPM1 and DNMT3A, n (%) | <.001 | |||
| Either or neither mutated | 57 (53) | 92 (90) | 90 (67) | |
| Both mutated | 51 (47) | 10 (10) | 44 (33) | |
| NPM1 and FLT3-ITD, n (%) | <.001 | |||
| Either or neither mutated | 83 (77) | 89 (90) | 80 (60) | |
| Both mutated | 25 (23) | 10 (10) | 54 (40) | |
| ERG expression group‡, n (%) | <.001 | |||
| High | 14 (12) | 75 (71) | 95 (66) | |
| Low | 100 (88) | 30 (29) | 48 (34) | |
| BAALC expression group‡, n (%) | <.001 | |||
| High | 15 (16) | 85 (82) | 68 (51) | |
| Low | 81 (84) | 19 (18) | 66 (49) | |
| MN1 expression group‡, n (%) | <.001 | |||
| High | 29 (27) | 77 (76) | 70 (50) | |
| Low | 79 (73) | 24 (24) | 70 (50) | |
| miR-181a expression group‡, n (%) | <.001 | |||
| High | 8 (8) | 81 (90) | 59 (54) | |
| Low | 87 (92) | 9 (10) | 51 (46) | |
| miR-3151 expression group‡, n (%) | <.001 | |||
| Expressed | 3 (3) | 36 (40) | 12 (11) | |
| Not expressed | 92 (97) | 54 (60) | 98 (89) | |
| miR-155 expression group‡, n (%) | <.001 | |||
| High | 33 (35) | 37 (41) | 77 (70) | |
| Low | 62 (65) | 53 (59) | 33 (30) |
| Characteristic . | Cluster 1 (n = 115) . | Cluster 2 (n = 106) . | Cluster 3 (n = 144) . | P . |
|---|---|---|---|---|
| Age, y | .02 | |||
| Median | 50 | 43 | 46 | |
| Range | 19-59 | 17-59 | 18-59 | |
| Sex, n (%) | .06 | |||
| Male | 64 (56) | 61 (58) | 63 (44) | |
| Female | 51 (44) | 45 (42) | 81 (56) | |
| Race, n (%) | .75 | |||
| White | 102 (90) | 97 (92) | 125 (89) | |
| Nonwhite | 11 (10) | 8 (8) | 15 (11) | |
| Hemoglobin, g/dL | .17 | |||
| Median | 9.1 | 9.5 | 9.1 | |
| Range | 4.8-25.1 | 4.2-13.6 | 4.9-14.4 | |
| Platelet count, ×109/L | <.001 | |||
| Median | 76 | 51 | 47 | |
| Range | 9-433 | 8-445 | 8-270 | |
| WBC count, ×109/L | <.001 | |||
| Median | 42.8 | 15.3 | 29.0 | |
| Range | 1.9-308.8 | 0.8-223.8 | 0.6-475.0 | |
| Blood blasts, % | <.001 | |||
| Median | 44 | 64 | 68 | |
| Range | 0-95 | 0-97 | 0-97 | |
| BM blasts, % | .31 | |||
| Median | 70 | 65 | 70 | |
| Range | 18-96 | 19-95 | 21-95 | |
| Extramedullary involvement, n (%) | .005 | |||
| Present | 47 (41) | 23 (22) | 36 (26) | |
| Absent | 67 (59) | 80 (78) | 103 (74) | |
| ASXL1, n (%) | .12 | |||
| Mutated | 1 (1) | 6 (6) | 5 (4) | |
| Wild type | 108 (99) | 95 (94) | 131 (96) | |
| CEBPA, n (%) | <.001 | |||
| Double mutated | 1 (1) | 40 (39) | 13 (9) | |
| Wild type | 106 (99) | 63 (61) | 125 (91) | |
| DNMT3A, n (%) | <.001 | |||
| Mutated | 63 (57) | 23 (22) | 53 (39) | |
| Wild type | 48 (43) | 81 (78) | 84 (61) | |
| FLT3-ITD, n (%) | <.001 | |||
| Present | 36 (32) | 19 (19) | 82 (57) | |
| Absent | 77 (68) | 83 (81) | 61 (43) | |
| FLT3-TKD, n (%) | .02 | |||
| Present | 18 (16) | 5 (5) | 13 (9) | |
| Absent | 77 (68) | 83 (81) | 61 (43) | |
| IDH1, n (%) | .11 | |||
| Mutated | 6 (5) | 13 (13) | 8 (6) | |
| Wild type | 105 (95) | 91 (88) | 129 (94) | |
| IDH2, n (%) | .20 | |||
| Mutated | 7 (6) | 14 (13) | 13 (9) | |
| Wild type | 104 (94) | 90 (87) | 124 (91) | |
| NPM1, n (%) | <.001 | |||
| Mutated | 86 (80) | 26 (25) | 89 (66) | |
| Wild type | 22 (20) | 76 (75) | 45 (34) | |
| RUNX1, n (%) | .03 | |||
| Mutated | 4 (4) | 11 (11) | 4 (3) | |
| Wild type | 107 (96) | 93 (89) | 133 (97) | |
| SF1, n (%) | .52 | |||
| Mutated | 1 (1) | 1 (1) | 0 (0) | |
| Wild type | 110 (99) | 103 (99) | 137 (100) | |
| SF3A1, n (%) | 1.00 | |||
| Mutated | 0 (0) | 0 (0) | 1 (1) | |
| Wild type | 111 (100) | 104 (100) | 136 (99) | |
| SF3B1, n (%) | .32 | |||
| Mutated | 3 (3) | 5 (5) | 2 (1) | |
| Wild type | 108 (97) | 99 (95 | 135 (99) | |
| SRSF2, n (%) | .22 | |||
| Mutated | 2 (2) | 6 (6) | 3 (2) | |
| Wild type | 109 (98) | 97 (94) | 133 (98) | |
| TET2, n (%) | .61 | |||
| Mutated | 15 (14) | 12 (12) | 13 (9) | |
| Wild type | 96 (86) | 92 (88) | 124 (91) | |
| U2AF1, n (%) | .11 | |||
| Mutated | 3 (3) | 1 (1) | 0 (0) | |
| Wild type | 108 (97) | 103 (99) | 137 (100) | |
| U2AF2, n (%) | NA* | |||
| Mutated | 0 (0) | 0 (0) | 0 (0) | |
| Wild type | 111 (100) | 104 (100) | 137 (100) | |
| WT1, n (%) | .007 | |||
| Mutated | 6 (5) | 9 (9) | 24 (18) | |
| Wild type | 105 (95) | 95 (91) | 113 (82) | |
| ZRSR2, n (%) | .85 | |||
| Mutated | 4 (4) | 4 (4) | 7 (5) | |
| Wild type | 107 (96) | 100 (96) | 130 (95) | |
| ELN genetic group†, n (%) | <.001 | |||
| Favorable | 75 (69) | 65 (65) | 59 (45) | |
| Intermediate | 20 (18) | 17 (17) | 51 (39) | |
| Adverse | 14 (13) | 18 (18) | 20 (15) | |
| NPM1 and DNMT3A, n (%) | <.001 | |||
| Either or neither mutated | 57 (53) | 92 (90) | 90 (67) | |
| Both mutated | 51 (47) | 10 (10) | 44 (33) | |
| NPM1 and FLT3-ITD, n (%) | <.001 | |||
| Either or neither mutated | 83 (77) | 89 (90) | 80 (60) | |
| Both mutated | 25 (23) | 10 (10) | 54 (40) | |
| ERG expression group‡, n (%) | <.001 | |||
| High | 14 (12) | 75 (71) | 95 (66) | |
| Low | 100 (88) | 30 (29) | 48 (34) | |
| BAALC expression group‡, n (%) | <.001 | |||
| High | 15 (16) | 85 (82) | 68 (51) | |
| Low | 81 (84) | 19 (18) | 66 (49) | |
| MN1 expression group‡, n (%) | <.001 | |||
| High | 29 (27) | 77 (76) | 70 (50) | |
| Low | 79 (73) | 24 (24) | 70 (50) | |
| miR-181a expression group‡, n (%) | <.001 | |||
| High | 8 (8) | 81 (90) | 59 (54) | |
| Low | 87 (92) | 9 (10) | 51 (46) | |
| miR-3151 expression group‡, n (%) | <.001 | |||
| Expressed | 3 (3) | 36 (40) | 12 (11) | |
| Not expressed | 92 (97) | 54 (60) | 98 (89) | |
| miR-155 expression group‡, n (%) | <.001 | |||
| High | 33 (35) | 37 (41) | 77 (70) | |
| Low | 62 (65) | 53 (59) | 33 (30) |
NA, not applicable.
P value could not be calculated because of 0 cell counts.
Among patients with CN-AML, the ELN favorable-risk category comprises patients with double-mutated CEBPA and patients with mutated NPM1 without FLT3-ITD or with FLT3-ITDlow. The ELN intermediate-risk category includes patients with wild-type or single-mutated CEBPA, patients with wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow, and/or patients with mutated NPM1 and FLT3-ITDhigh. The ELN adverse-risk category comprises patients with wild-type or single-mutated CEBPA and wild-type NPM1 with FLT3-ITDhigh, patients with mutated RUNX1 and/or ASXL1 (if these mutations do not co-occur with favorable-risk subtypes), and/or patients with mutated TP53. FLT3-ITDlow is defined by an FLT3-ITD/FLT3 wild-type allelic ratio of <0.5, and FLT3-ITDhigh is defined by an FLT3-ITD/FLT3 wild-type allelic ratio of equal to or more than 0.5.
The median expression value was used as a cut point.