AML and related neoplasms and acute leukemias of ambiguous lineage
| AML and related neoplams . | |
|---|---|
| AML with recurrent genetic abnormalities (requiring ≥10% blasts in BM or PB)* • APL with t(15;17)(q24.1;q21.2)/PML::RARA† • AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11 • AML with t(9;11)(p21.3;q23.3)/MLLT3::KMT2A‡ • AML with t(6;9)(p22.3;q34.1)/DEK::NUP214 • AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2, MECOM(EVI1)§ • AML with other rare recurring translocations‖ • AML with mutated NPM1 • AML with in-frame bZIP mutated CEBPA¶ • AML with t(9;22)(q34.1;q11.2)/BCR::ABL1* | Myeloid sarcoma Acute leukemia of ambiguous lineage • Acute undifferentiated leukemia • MPAL with t(9;22)(q34.1;q11.2)/BCR::ABL1 • MPAL with t(v;11q23.3)/KMT2A-rearranged • MPAL, B/myeloid, not otherwise specified • MPAL, T/myeloid, not otherwise specified |
| Categories designated AML (if ≥20% blasts in BM or PB) or MDS/AML (if 10-19% blasts in BM or PB) • AML with mutated TP53# • AML with myelodysplasia-related gene mutations Defined by mutations in ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 • AML with myelodysplasia-related cytogenetic abnormalities** • AML not otherwise specified | Myeloid proliferations related to Down syndrome • Transient abnormal myelopoiesis associated with Down syndrome • Myeloid leukemia associated with Down syndrome Blastic plasmacytoid dendritic cell neoplasm |
| Diagnostic qualifiers†† Therapy-related‡‡ • Prior chemotherapy, radiotherapy, immune interventions Progressed from MDS • MDS should be confirmed by standard diagnostics and >3 mo prior to AML diagnosis Progressed from MDS/MPN (specify type) • MDS/MPN should be confirmed by standard diagnostics and >3 mo prior to AML diagnosis Germline predisposition (specify type) | |
| AML and related neoplams . | |
|---|---|
| AML with recurrent genetic abnormalities (requiring ≥10% blasts in BM or PB)* • APL with t(15;17)(q24.1;q21.2)/PML::RARA† • AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11 • AML with t(9;11)(p21.3;q23.3)/MLLT3::KMT2A‡ • AML with t(6;9)(p22.3;q34.1)/DEK::NUP214 • AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2, MECOM(EVI1)§ • AML with other rare recurring translocations‖ • AML with mutated NPM1 • AML with in-frame bZIP mutated CEBPA¶ • AML with t(9;22)(q34.1;q11.2)/BCR::ABL1* | Myeloid sarcoma Acute leukemia of ambiguous lineage • Acute undifferentiated leukemia • MPAL with t(9;22)(q34.1;q11.2)/BCR::ABL1 • MPAL with t(v;11q23.3)/KMT2A-rearranged • MPAL, B/myeloid, not otherwise specified • MPAL, T/myeloid, not otherwise specified |
| Categories designated AML (if ≥20% blasts in BM or PB) or MDS/AML (if 10-19% blasts in BM or PB) • AML with mutated TP53# • AML with myelodysplasia-related gene mutations Defined by mutations in ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 • AML with myelodysplasia-related cytogenetic abnormalities** • AML not otherwise specified | Myeloid proliferations related to Down syndrome • Transient abnormal myelopoiesis associated with Down syndrome • Myeloid leukemia associated with Down syndrome Blastic plasmacytoid dendritic cell neoplasm |
| Diagnostic qualifiers†† Therapy-related‡‡ • Prior chemotherapy, radiotherapy, immune interventions Progressed from MDS • MDS should be confirmed by standard diagnostics and >3 mo prior to AML diagnosis Progressed from MDS/MPN (specify type) • MDS/MPN should be confirmed by standard diagnostics and >3 mo prior to AML diagnosis Germline predisposition (specify type) | |
Classification adopted from reference 2. BM, bone marrow; MPAL, mixed phenotype acute leukemia.
Bone marrow or peripheral blood blast count of ≥ 10% required, except for AML with t(9;22)(q34.1;q11.2)/BCR::ABL1 which requires bone marrow or peripheral blood blast count of ≥ 20% due to its overlap with progression of chronic myeloid leukemia, BCR::ABL1-positive.
Other recurring translocations involving RARA should be reported accordingly: eg, APL with t(1;17)(q42.3;q21.2)/IRF2BP2::RARA; APL with t(5;17)(q35.1;q21.2)/NPM1::RARA; APL with t(11;17)(q23.2;q21.2)/ZBTB16::RARA; APL with cryptic inv(17) or del(17)(q21.2q21.2)/STAT5B::RARA; STAT3::RARA; other genes rarely rearranged with RARA: TBL1XR1 (3q26.3); FIP1L1 (4q12); BCOR (Xp11.4).
Other recurring translocations involving KMT2A should be reported accordingly: eg, AML with t(4;11)(q21.3;q23.3)/AFF1::KMT2A; AML with t(6;11)(q27;q23.3)/AFDN::KMT2A; AML with t(10;11)(p12.3;q23.3)/MLLT10::KMT2A; AML with t(10;11)(q21.3;q23.3)/TET1::KMT2A; AML with t(11;19)(q23.3;p13.1)/KMT2A::ELL; AML with t(11;19)(q23.3;p13.3)/KMT2A::MLLT1.
Other recurring translocations involving MECOM should be reported accordingly: eg, AML with t(2;3)(p11∼23;q26.2)/MECOM::?; AML with t(3;8)(q26.2;q24.2)/MYC, MECOM; AML with t(3;12)(q26.2;p13.2)/ETV6::MECOM; AML with t(3;21)(q26.2;q22.1)/MECOM::RUNX1.
Other rare recurring translocations: AML with t(1;3)(p36.3;q21.3)/PRDM16::RPN1; AML (megakaryoblastic) with t(1;22)(p13.3;q13.1)/RBM15::MRTFA; AML with t(3;5)(q25.3;q35.1)/NPM1::MLF1; AML with t(5;11)(q35.2;p15.4)/NUP98::NSD1; AML with t(7;12)(q36.3;p13.2)/ETV6::MNX1; AML with t(8;16)(p11.2;p13.3)/KAT6A::CREBBP; AML with t(10;11)(p12.3;q14.2)/PICALM::MLLT10; AML with t(11;12)(p15.4;p13.3)/NUP98::KMD5A; AML with NUP98 and other partners; AML with t(16;21)(p11.2;q22.2)/FUS::ERG; AML with t(16;21)(q24.3;q22.1)/RUNX1::CBFA2T3; AML with inv(16)(p13.3q24.3)/CBFA2T3::GLIS2.
AML with in-frame mutation in the bZIP domain of the CEBPA gene, either monoallelic or biallelic.
The presence of a pathogenic somatic TP53 mutation (at a variant allele fraction of at least 10%, with or without loss of the wild-type TP53 allele) defines the entity AML with mutated TP53.
Cytogenetic abnormalities sufficient for the diagnosis of AML with MDS-related cytogenetic abnormalities and the absence of other AML-defining disease categories. Complex karyotype: ≥3 unrelated chromosome abnormalities in the absence of other class-defining recurring genetic abnormalities; excludes hyperdiploid karyotypes with three or more trisomies (or polysomies) without structural abnormalities. Unbalanced clonal abnormalities: del(5q)/t(5q)/add(5q); −7/del(7q); +8; del(12p)/t(12p)/(add)(12p); i(17q), −17/add(17p) or del(17p); del(20q); and/or idic(X)(q13).
Examples: AML with myelodysplasia-related cytogenetic abnormality, therapy-related; AML with myelodysplasia-related gene mutation, prior myelodysplastic syndrome; AML with myelodysplasia-related gene mutation, germline RUNX1 mutation.
Prior therapy for nonmyeloid neoplasms.