Table 1.

Mutations in CEBPA, FLT3, IDH1, IDH2, or NPM1 detected at diagnosis

Number of patientscDNAProteinVAF∗ Comutations (VAF, %)
CEBPA (n = 7)     
1 c.998G>C p.(Arg333Pro)†  5.4 DNMT3A (38.5), FLT3 (7.7), NPM1 (38.2), IDH1 (18.5) 
1 c.971T>A p.(Leu324Gln)†  33.05 EZH2 (55.07), ETV6 (50.09), PTPN11 (12.54),
SRSF2 (34.94) 
1 c.890G>T p.(Arg297Leu)†  7.38 TET2 (42.44), EZH2 (84.39), ASXL1 (43), RUNX1 (24.3, 6.76, 23.17), ZRSR2 (87.65), STAG2 (13.31, 11.47) 
1 c.48_49insGGCTAA p.(Ser16.Ser17insGlyTer) 4 SRSF2 (46.1), ASXL1 (46.8), CBL (1), TET2 (47.4, 45.3) 
 c.700_710dup p.(Pro239fs) 31.2  
1 c.988C>T p.(Gln330Ter)‡  42.94 None 
 c.325_326insGCGGGCGTAAAAAACTACC p.(Pro109fs) 41.4  
1 c.767T>A p.(Leu256Gln) 27.72 CSF3R (20.63), EZH2 (86.22), NF1 (25.68), ZRSR2 (84.85), RUNX1 (40.98, 4.17) 
1 c.950T>A p.(Leu317Gln)†  27.93 ASXL1 (48), RUNX1 (31.51, 9.16) 
FLT3§ (n = 8)     
6 TKD  
1 c.2503G>T p.(Asp835Tyr)||  30.36 DNMT3 (46.48), NPM1 (37.04) 
1 c.2516A>G p.(Asp839Gly)||  7.7 CEBPA (5.4), DNMT3A (38.5), NPM1 (38.20), IDH1 (18.5) 
1 c.1879G>A p.(Ala627Thr)  51.41 TET2 (46.92), NPM1 (40.58), FLT3-ITD (11.64, 21 bp) 
1 c.A1993C p.(Met665Leu)  13.87 DNMT3A (50.42), MTOR (9.21), KRAS (25.81), NPM1 (38.71) 
 c.G1992A p.(Met664Ile)  13.55  
1 c.T1771G p.(Tyr591Asp)  25.71 NRAS (2.83), CUX1 (47.03), KMT2D (45.91), SRSF2 (43.08), ASXL1 (43.32), BCORL1 (95.18) 
 c.A1715G p.(Tyr572Cys)  28.9  
1 c.1852T>C p.(Ser618Pro)  50.22 JAK2 (3.68), TET2 (88.37), ASXL1 (49.81) 
3 ITD 11.6 (5.5-30) 

  • Patient 1: DNMT3A (36.69), U2AF1 (41.7), SF3B1 (39.75)

  • Patient 2: NPM1 (37.28), DNMT3A (34.15), SF3B1 (41.6), PDGFRB (40.14)

  • Patient 3: TET2 (46.92), NPM1 (40.58), FLT3-TKD (51.41)

 
IDH1 (n = 12)     
5 c.395G>A p.(Arg132His) 25 (16-45) 

  • Patient 1: CEBPA (5.4), DNMT3A (38.5), FLT3-TKD (7.7), NPM1 (38.20)

  • Patient 2: SRSF2 (37.87), RUNX1 (34.8%)

  • Patient 3: DNMT3A (39.8), TET2 (38.3)

  • Patient 4: ASXL1 (33.60), SRSF2 (15.94), TET2 (27.13)

  • Patient 5: ASXL1 (10, 23), SRSF2 (43)

 
3 c.394C>T p.(Arg132Cys) 13 (5-21) 

  • Patient 1: NRAS (3.71), TET2 (50.87, 44.59, 47.77), EZH2 (92.79), RUNX1 (20.48), STAG2 (6.52)

  • Patient 2: RUNX1 (16.38), STAG1 (16.98)

  • Patient 3: RUNX1 (2.15), SRSF2 (44), TET2 (45.3, 18.5, 4.4)

 
1 c.298C>T p.(Arg100Ter) 51.75 ASXL1 (32.8), RUNX1 (32.8), SRSF2 (50.5), STAG2 (10.3) 
1 c.122+2T>G Splice site 18.2 SRSF2 (11.2, 21.8), TET2 (45.4, 43.3) 
2 Not available 
IDH2 (n = 26)     
26 c.419G>A p.(Arg140Gln) 41 (1.9-50) 

  • Patient 1: ASXL1 (27.5), U2AF1 (44.5)

  • Patient 2: ASXL1 (36.9), KRAS (43.3), SRSF2 (46.8)

  • Patient 3: ASXL1 (40), SRSF2 (44), STAG2 (45)

  • Patient 4: JAK2 (35.1)

  • Patient 5: SRSF2 (47), TET2 (21)

  • Patient 6: ASXL1 (40.2), SRSF2 (50), TET2 (42.2)

  • Patient 7: DNMT3A (1.98), SF3B1 (7.3)

  • Patient 8: ASXL1 (22), JAK2 (3.6), SH2B3 (48.5, 22.6), SRSF2 (44.4)

  • Patient 9: SRSF2 (42)

  • Patient 10: SRSF2 (47.2), JAK2 (47.6), CBL (94.6)

  • Patient 11: ASXL1 (24), TET2 (4.6), U2AF1 (48)

  • Patient 12: SRSF2 (34.32), EZH2 (8.66), ETNK1 (32.17)

  • Patient 13: JAK2 (4.12), ASXL1 (46.92), CBL (24.1), SRSF2 (58.84, 44.12, 43.11)

  • Patient 14: U2AF1 (43), MPL (25), ZRSR2 (38)

  • Patient 15: ASXL1 (29), U2AF1 (46.44), ZRSR2 (44)

  • Patient 16: DNMT3A (40), NPM1 (34.45), NF1 (50), SETBP1 (45.36)

  • Patient 17: DNMT3A (36.09), NPM1 (33.13)

  • Patient 18: CSF3R (16.26), CDH23 (45.45), SH2B3 (50.54), SETBP1 (20), STAG2 (29.6, 12.31)

  • Patient 19: DNMT3A (51.9)

  • Patient 20: JAK2 (88.4), SRSF2 (53.2)

  • Patient 21: ZRSR2 (84.6), TET2 (48.2), MPL (48.5)

  • Patient 22: ZRSR2 (86.62)

  • Patient 23: ASXL1 (38.82), SRSF2 (47.93)

  • Patient 24: KRAS (23.81)

  • Patient 25: CBL (4.45), KRAS (3.98, 8.58), SRSF2 (50.07)

  • Patient 26: ASXL1 (36.27, 11.36), U2AF1 (46.82), ZRSR2 (35.95)

 
NPM1 (n = 11)     
6 c.863_864insTCTG p.(Trp288CysfsTer12) 41 (37-47) 

  • Patient 1: DNMT3 (41.5, 46.48), FLT3-TKD (30.36)

  • Patient 2: CEBPA (5.4), DNMT3A (38.5), FLT3-TKD (7.7), IDH1 (18.5)

  • Patient 3: TET2 (46.92), FLT3-TKD (51.41), FLT3-ITD (11.64)

  • Patient 4: DNMT3A (44.42, 48.80)

  • Patient 5: SF3B1 (49)

  • Patient 6: DNMT3A (NA), NRAS (NA)

 
4 c.772_773insTCTG p.(Leu258fs) 5.6 (33-39) 

  • Patient 1: DNMT3A (50.4), MTOR (9.21), KRAS (25.81), FLT3-TKD (13.87, 13.55)

  • Patient 2: FLT3-ITD (5.45), DNMT3A (34.15), SF3B1 (41.6), PDGFRB (40.14)

  • Patient 3: DNMT3A (40), IDH2 (38.04), NF1 (50), SETBP1 (45.36)

  • Patient 4: DNMT3A (36.09), IDH2 (37.96%)

 
1 c.861_862insTGCA p.(Leu287fs) 30.77 PTPN11 (23.37), WT1 (18.43) 
Number of patientscDNAProteinVAF∗ Comutations (VAF, %)
CEBPA (n = 7)     
1 c.998G>C p.(Arg333Pro)†  5.4 DNMT3A (38.5), FLT3 (7.7), NPM1 (38.2), IDH1 (18.5) 
1 c.971T>A p.(Leu324Gln)†  33.05 EZH2 (55.07), ETV6 (50.09), PTPN11 (12.54),
SRSF2 (34.94) 
1 c.890G>T p.(Arg297Leu)†  7.38 TET2 (42.44), EZH2 (84.39), ASXL1 (43), RUNX1 (24.3, 6.76, 23.17), ZRSR2 (87.65), STAG2 (13.31, 11.47) 
1 c.48_49insGGCTAA p.(Ser16.Ser17insGlyTer) 4 SRSF2 (46.1), ASXL1 (46.8), CBL (1), TET2 (47.4, 45.3) 
 c.700_710dup p.(Pro239fs) 31.2  
1 c.988C>T p.(Gln330Ter)‡  42.94 None 
 c.325_326insGCGGGCGTAAAAAACTACC p.(Pro109fs) 41.4  
1 c.767T>A p.(Leu256Gln) 27.72 CSF3R (20.63), EZH2 (86.22), NF1 (25.68), ZRSR2 (84.85), RUNX1 (40.98, 4.17) 
1 c.950T>A p.(Leu317Gln)†  27.93 ASXL1 (48), RUNX1 (31.51, 9.16) 
FLT3§ (n = 8)     
6 TKD  
1 c.2503G>T p.(Asp835Tyr)||  30.36 DNMT3 (46.48), NPM1 (37.04) 
1 c.2516A>G p.(Asp839Gly)||  7.7 CEBPA (5.4), DNMT3A (38.5), NPM1 (38.20), IDH1 (18.5) 
1 c.1879G>A p.(Ala627Thr)  51.41 TET2 (46.92), NPM1 (40.58), FLT3-ITD (11.64, 21 bp) 
1 c.A1993C p.(Met665Leu)  13.87 DNMT3A (50.42), MTOR (9.21), KRAS (25.81), NPM1 (38.71) 
 c.G1992A p.(Met664Ile)  13.55  
1 c.T1771G p.(Tyr591Asp)  25.71 NRAS (2.83), CUX1 (47.03), KMT2D (45.91), SRSF2 (43.08), ASXL1 (43.32), BCORL1 (95.18) 
 c.A1715G p.(Tyr572Cys)  28.9  
1 c.1852T>C p.(Ser618Pro)  50.22 JAK2 (3.68), TET2 (88.37), ASXL1 (49.81) 
3 ITD 11.6 (5.5-30) 

  • Patient 1: DNMT3A (36.69), U2AF1 (41.7), SF3B1 (39.75)

  • Patient 2: NPM1 (37.28), DNMT3A (34.15), SF3B1 (41.6), PDGFRB (40.14)

  • Patient 3: TET2 (46.92), NPM1 (40.58), FLT3-TKD (51.41)

 
IDH1 (n = 12)     
5 c.395G>A p.(Arg132His) 25 (16-45) 

  • Patient 1: CEBPA (5.4), DNMT3A (38.5), FLT3-TKD (7.7), NPM1 (38.20)

  • Patient 2: SRSF2 (37.87), RUNX1 (34.8%)

  • Patient 3: DNMT3A (39.8), TET2 (38.3)

  • Patient 4: ASXL1 (33.60), SRSF2 (15.94), TET2 (27.13)

  • Patient 5: ASXL1 (10, 23), SRSF2 (43)

 
3 c.394C>T p.(Arg132Cys) 13 (5-21) 

  • Patient 1: NRAS (3.71), TET2 (50.87, 44.59, 47.77), EZH2 (92.79), RUNX1 (20.48), STAG2 (6.52)

  • Patient 2: RUNX1 (16.38), STAG1 (16.98)

  • Patient 3: RUNX1 (2.15), SRSF2 (44), TET2 (45.3, 18.5, 4.4)

 
1 c.298C>T p.(Arg100Ter) 51.75 ASXL1 (32.8), RUNX1 (32.8), SRSF2 (50.5), STAG2 (10.3) 
1 c.122+2T>G Splice site 18.2 SRSF2 (11.2, 21.8), TET2 (45.4, 43.3) 
2 Not available 
IDH2 (n = 26)     
26 c.419G>A p.(Arg140Gln) 41 (1.9-50) 

  • Patient 1: ASXL1 (27.5), U2AF1 (44.5)

  • Patient 2: ASXL1 (36.9), KRAS (43.3), SRSF2 (46.8)

  • Patient 3: ASXL1 (40), SRSF2 (44), STAG2 (45)

  • Patient 4: JAK2 (35.1)

  • Patient 5: SRSF2 (47), TET2 (21)

  • Patient 6: ASXL1 (40.2), SRSF2 (50), TET2 (42.2)

  • Patient 7: DNMT3A (1.98), SF3B1 (7.3)

  • Patient 8: ASXL1 (22), JAK2 (3.6), SH2B3 (48.5, 22.6), SRSF2 (44.4)

  • Patient 9: SRSF2 (42)

  • Patient 10: SRSF2 (47.2), JAK2 (47.6), CBL (94.6)

  • Patient 11: ASXL1 (24), TET2 (4.6), U2AF1 (48)

  • Patient 12: SRSF2 (34.32), EZH2 (8.66), ETNK1 (32.17)

  • Patient 13: JAK2 (4.12), ASXL1 (46.92), CBL (24.1), SRSF2 (58.84, 44.12, 43.11)

  • Patient 14: U2AF1 (43), MPL (25), ZRSR2 (38)

  • Patient 15: ASXL1 (29), U2AF1 (46.44), ZRSR2 (44)

  • Patient 16: DNMT3A (40), NPM1 (34.45), NF1 (50), SETBP1 (45.36)

  • Patient 17: DNMT3A (36.09), NPM1 (33.13)

  • Patient 18: CSF3R (16.26), CDH23 (45.45), SH2B3 (50.54), SETBP1 (20), STAG2 (29.6, 12.31)

  • Patient 19: DNMT3A (51.9)

  • Patient 20: JAK2 (88.4), SRSF2 (53.2)

  • Patient 21: ZRSR2 (84.6), TET2 (48.2), MPL (48.5)

  • Patient 22: ZRSR2 (86.62)

  • Patient 23: ASXL1 (38.82), SRSF2 (47.93)

  • Patient 24: KRAS (23.81)

  • Patient 25: CBL (4.45), KRAS (3.98, 8.58), SRSF2 (50.07)

  • Patient 26: ASXL1 (36.27, 11.36), U2AF1 (46.82), ZRSR2 (35.95)

 
NPM1 (n = 11)     
6 c.863_864insTCTG p.(Trp288CysfsTer12) 41 (37-47) 

  • Patient 1: DNMT3 (41.5, 46.48), FLT3-TKD (30.36)

  • Patient 2: CEBPA (5.4), DNMT3A (38.5), FLT3-TKD (7.7), IDH1 (18.5)

  • Patient 3: TET2 (46.92), FLT3-TKD (51.41), FLT3-ITD (11.64)

  • Patient 4: DNMT3A (44.42, 48.80)

  • Patient 5: SF3B1 (49)

  • Patient 6: DNMT3A (NA), NRAS (NA)

 
4 c.772_773insTCTG p.(Leu258fs) 5.6 (33-39) 

  • Patient 1: DNMT3A (50.4), MTOR (9.21), KRAS (25.81), FLT3-TKD (13.87, 13.55)

  • Patient 2: FLT3-ITD (5.45), DNMT3A (34.15), SF3B1 (41.6), PDGFRB (40.14)

  • Patient 3: DNMT3A (40), IDH2 (38.04), NF1 (50), SETBP1 (45.36)

  • Patient 4: DNMT3A (36.09), IDH2 (37.96%)

 
1 c.861_862insTGCA p.(Leu287fs) 30.77 PTPN11 (23.37), WT1 (18.43) 

cDNA, complementary DNA; NA, not available; VAF, variant allele frequency.

∗

For mutations present in >1 patient, we show VAF median and range. For mutations present in only 1 patient, we show %VAF.

†

CEBPA in-frame point mutations in the bZIP region (n = 4).

‡

CEBPA mutations in the bZIP region (n = 5).

§

One patient had both FLT3-ITD and FLT3-TKD.

||

FLT3-TKD2 variants (n = 2).

FLT3-TKD1 variants (n = 6).

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