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Gene Symbol KMT2A
Synonyms ALL-1 | CXXC7 | HRX | HTRX1 | MLL | MLL1 | MLL1A | TRX1 | WDSTS
Gene Description KMT2A, lysine methyltransferase 2A, also referred to as MLL, is a transcriptional coactivator that epigenetically regulates gene transcription via methylation and is primarily associated with hematopoietic and embyronic development (PMID: 26161385). KMT2A translocations are frequently observed in specific leukemias including acute myeloid, acute lymphoblastic, and mixed lineage (PMID: 17957188, PMID: 32243611).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KMT2A fusion acute myeloid leukemia sensitive I-BET151 + SGC0946 Preclinical - Patient cell culture Actionable In a preclinical study, I-BET151 and SGC0946 synergistically inhibited proliferation of patient-derived acute myeloid leukemia cells harboring KMT2A fusions in culture (PMID: 27294782). 27294782
KMT2A fusion acute myeloid leukemia predicted - sensitive MI-503 Preclinical - Cell culture Actionable In a preclinical study, MI-503 inhibited growth of several acute myeloid leukemia (AML) cell lines and primary AML samples harboring KMT2A (MLL) fusions in culture (PMID: 25817203). 25817203
KMT2A fusion acute myeloid leukemia sensitive CDKI-73 Preclinical - Cell line xenograft Actionable In a preclinical study, CDKI-73 treatment inhibited Cdk9 kinase activity and viability, and induced apoptosis in acute myeloid leukemia cell lines harboring KMT2A fusions in culture, and inhibited tumor growth and induced regression in a cell line xenograft model (PMID: 30194564). 30194564
KMT2A - AFDN acute myeloid leukemia predicted - sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KMT2A-AFDN was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating decreased cell viability (PMID: 32645016). 32645016
KMT2A - AFF1 acute myeloid leukemia sensitive Dinaciclib Preclinical Actionable In a preclinical study, treatment with Dinaciclib resulted in induced cell death of acute myeloid leukemia cells harboring KMT2A-AFF1 in culture (PMID: 26627013). 26627013
KMT2A - AFF1 acute lymphoblastic leukemia predicted - sensitive AZD5153 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD5153 inhibited proliferation of acute lymphocytic leukemia cells harboring KMT2A-AFF1 (MLL-AF4) in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27573426). 27573426
KMT2A - AFF1 acute myeloid leukemia predicted - sensitive AZD5153 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD5153 inhibited proliferation of acute myeloid leukemia cells harboring KMT2A-AFF1 (MLL-AF4) in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27573426). 27573426
KMT2A - AFF1 leukemia sensitive IRAK1/4 Preclinical - Cell culture Actionable In a preclinical study, leukemia cells harboring KMT2A-AFF1 demonstrated sensitivity to IRAK1/4 in culture, resulting in decreased cell proliferation (PMID: 28065413). 28065413
KMT2A - AFF1 leukemia sensitive I-BET151 + SGC0946 Preclinical - Cell culture Actionable In a preclinical study, I-BET151 and SGC0946 synergistically inhibited proliferation of leukemia cells harboring KMT2A-AFF1 in culture (PMID: 27294782). 27294782
KMT2A - AFF1 acute myeloid leukemia sensitive MI-503 Preclinical - Cell line xenograft Actionable In a preclinical study, MI-503 reduced expression of KMT2A (MLL) fusion target genes, inhibited growth of an acute myeloid leukemia (AML) cell lines harboring KMT2A-AFF1 (MLL-AF4) in culture, and inhibited tumor growth and progression in an AML cell line xenograft model harboring KMT2A-AFF1 (MLL-AF4) (PMID: 25817203). 25817203
KMT2A - AFF1 B-cell acute lymphoblastic leukemia predicted - resistant Blinatumomab Case Reports/Case Series Actionable In a clinical case study, Blincyto (blinatumomab) treatment in a patient with B-lymphoblastic leukemia harboring KMT2A-AFF1 resulted in lineage switch as demonstrated by identification of myeloid sarcoma of the breast and acute myeloid leukemia within one month of treatment onset, along with mixed phenotype acute leukemia observed following cessation of treatment (PMID: 31885955). 31885955
KMT2A - AFF1 acute myeloid leukemia predicted - sensitive Tranylcypromine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, the addition of Parnate (tranylcypromine) resulted in increased sensitivity to Tretinoin treatment in acute myeloid leukemia cells harboring a KMT2A-AFF1 fusion (also known as MLL-AF4), with inhibition of cell growth and CD11b expression in culture (Blood (2012) 120 (21): 1345.). detail...
KMT2A - AFF1 acute myeloid leukemia predicted - sensitive Decitabine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, combination treatment of Tretinoin and Dacogen (decitabine) resulted in growth inhibition in acute myeloid leukemia cells harboring a KMT2A-AFF1 fusion in cell culture (PMID: 23063977). 23063977
KMT2A - AFF1 acute lymphoblastic leukemia sensitive I-BET151 Preclinical - Pdx & cell culture Actionable In a preclinical study, treatment with I-BET151 in acute lymphoblastic leukemia cell lines harboring a KMT2A-AFF1 fusion resulted in growth inhibition, cell cycle arrest, increased apoptosis, and down-regulation of BRD4 targets CDK6, c-MYC, and BCL2 in culture, and resulted in reduced leukemic engraftment and decreased disease burden in a patient-derived xenograft (PDX) model and prolonged survival and reduced cellularity in a cell line xenograft model (PMID: 29748211). 29748211
KMT2A - AFF1 acute lymphoblastic leukemia predicted - sensitive I-BET151 + Panobinostat Preclinical - Cell line xenograft Actionable In a preclinical study, acute lymphoblastic leukemia cell line xenograft models harboring a KMT2A-AFF1 fusion treated with a combination therapy of I-BET151 and Farydak (panobinostat) demonstrated reduced cellularity and a prolonged survival of 34 days compared to 28 days for mice receiving either I-BET151 alone or 21 days for those treated with control (PMID: 29748211). 29748211
KMT2A - AFF1 acute lymphoblastic leukemia predicted - sensitive I-BET151 + Prednisolone Preclinical - Cell culture Actionable In a preclinical study, treatment with I-BET151 enhanced the efficacy of Omnipred (prednisolone) in acute lymphoblastic leukemia cells harboring a KMT2A-AFF1 (also known as MLL-AF4) fusion, resulting in increased cell death compared to either therapy alone in culture (PMID: 29748211). 29748211
KMT2A - AFF1 acute lymphoblastic leukemia predicted - sensitive Givinostat + I-BET151 Preclinical - Cell culture Actionable In a preclinical study, combination therapy of I-BET151 and Givinostat (ITF2357) in acute lymphoblastic leukemia cell lines harboring a KMT2A-AFF1 fusion resulted in either a synergistic or additive effect, demonstrating increased apoptosis compared to either therapy alone in cell culture (PMID: 29748211). 29748211
KMT2A - AFF1 FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KMT2A-AFF1 and a FLT3-ITD was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating decreased cell viability (PMID: 32645016). 32645016
KMT2A - AFF4 leukemia predicted - sensitive Tranylcypromine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, the addition of Parnate (tranylcypromine) resulted in increased sensitivity to Tretinoin treatment in a murine leukemic cell line harboring a KMT2A-AFF4 fusion (also known as MLL-AF5q31), with inhibition of cell growth and CD11b expression in culture (Blood (2012) 120 (21): 1345.). detail...
KMT2A - AFF4 leukemia predicted - sensitive Abemaciclib Preclinical - Cell culture Actionable In a preclinical study, treatment with Verzenio (abemaciclib) induced apoptosis, reduced expression of Brd4 and Brd4-regulated proteins, including c-Myc, Cdk6, and Bcl-2, and resulted in an anti-tumor effect by inducing cell cycle arrest in leukemia cells harboring a KMT2A-AFF4 fusion that had developed resistance to Birabresib (OTX015) in culture (Cancer Res 2020;80(16 Suppl):Abstract nr 643.) detail...
KMT2A - AFF4 leukemia no benefit Decitabine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, combination treatment of Tretinoin and Dacogen (decitabine) in murine leukemic cells expressing a KMT2A-AFF4 fusion did not result in upregulation of Mac-1 and C/EBPalpha and resulted in similar growth compared to untreated cells in culture (PMID: 23063977). 23063977
KMT2A - AFF4 leukemia no benefit Tretinoin Preclinical - Cell culture Actionable In a preclinical study, treatment with Tretinoin in murine leukemic cells expressing a KMT2A-AFF4 fusion did not result in upregulation of Mac-1 and C/EBPalpha and resulted in similar growth compared to untreated cells in culture (PMID: 23063977). 23063977
KMT2A - ELL acute myeloid leukemia sensitive I-BET151 + SGC0946 Preclinical - Patient cell culture Actionable In a preclinical study, I-BET151 and SGC0946 synergistically inhibited proliferation of patient-derived acute myeloid leukemia cells harboring KMT2A-ELL in culture (PMID: 27294782). 27294782
KMT2A - EP300 acute myeloid leukemia sensitive MI-503 Preclinical - Patient cell culture Actionable In a preclinical study, MI-503 inhibited growth of a primary acute myeloid sample harboring KMT2A-EP300 in culture (PMID: 25817203). 25817203
KMT2A - GAS7 leukemia sensitive AMI-408 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with AMI-408 decreased growth of leukemia cells expressing KMT2A-GAS7 (MLL-GAS7) in culture, and increased survival in xenograft models (PMID: 26766589). 26766589
KMT2A - MLLT1 acute myeloid leukemia sensitive MI-503 Preclinical - Cell culture Actionable In a preclinical study, MI-503 inhibited growth of an acute myeloid leukemia cell line harboring KMT2A-MLLT1 (MLL-ENL) in culture (PMID: 25817203). 25817203
KMT2A - MLLT1 acute lymphoblastic leukemia predicted - sensitive I-BET151 + Prednisolone Preclinical - Cell culture Actionable In a preclinical study, treatment with I-BET151 enhanced the efficacy of Omnipred (prednisolone) in acute lymphoblastic leukemia cells harboring a KMT2A-MLLT1 (also known as MLL-ENL) fusion, resulting in increased cell death compared to either therapy alone in culture (PMID: 29748211). 29748211
KMT2A - MLLT1 NRAS G12D acute myeloid leukemia sensitive Dinaciclib Preclinical Actionable In a preclinical study, acute myeloid leukemia cells co-harboring KMT2A-MLLT1 and NRAS G12D demonstrated a decrease in tumor burden, reduced colony formation, and an increase in cell death when treated with Dinaciclib in both culture and mouse models (PMID: 26627013). 26627013
KMT2A - MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZD0156 Preclinical Actionable In a preclinical study, AZD0156 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
KMT2A - MLLT1 NRAS G12D acute myeloid leukemia predicted - sensitive AZ20 Preclinical Actionable In a preclinical study, AZ20 treatment resulted in growth inhibition of tumor cells and prolonged survival in animal models of acute myeloid leukemia harboring KMT2A-MLLT1 fusion and NRAS G12D (PMID: 27625305). 27625305
KMT2A - MLLT10 leukemia sensitive EPZ004777 Preclinical Actionable In a preclinical study, transformed cells expressing the fusion, KMT2A-MLLT10, demonstrated sensitivity to EPZ004777 in culture and in mouse models, resulting in cell cycle arrest, increased apoptotic activity, and inhibition of cell proliferation (PMID: 23138183). 23138183
KMT2A - MLLT10 acute myeloid leukemia sensitive I-BET151 + SGC0946 Preclinical - Patient cell culture Actionable In a preclinical study, I-BET151 and SGC0946 synergistically inhibited proliferation of patient-derived acute myeloid leukemia cells harboring KMT2A-MLLT10 in culture (PMID: 27294782). 27294782
KMT2A - MLLT3 acute myeloid leukemia sensitive Dinaciclib Preclinical Actionable In a preclinical study, treatment with Dinaciclib resulted in induced cell death of acute myeloid leukemia cells harboring KMT2A-MLLT3 in culture (PMID: 26627013). 26627013
KMT2A - MLLT3 leukemia sensitive IRAK1/4 Preclinical Actionable In a preclinical study, a transgenic leukemic mouse model harboring KMT2A-MLLT3 demonstrated sensitivity to IRAK1/4, resulting in delayed progression and improved survival (PMID: 28065413). 28065413
KMT2A - MLLT3 acute myeloid leukemia sensitive I-BET151 + SGC0946 Preclinical - Patient cell culture Actionable In a preclinical study, I-BET151 and SGC0946 synergistically inhibited proliferation of patient-derived acute myeloid leukemia cells harboring KMT2A-MLLT3 in culture, and prolonged survival in animal models of mouse KMT2A-MLLT3-positive leukemia (PMID: 27294782). 27294782
KMT2A - MLLT3 acute myeloid leukemia sensitive MI-503 Preclinical - Patient cell culture Actionable In a preclinical study, MI-503 inhibited growth of an acute myeloid leukemia (AML) cell line and primary AML samples harboring KMT2A-MLLT3 (MLL-AF9) in culture (PMID: 25817203). 25817203
KMT2A - MLLT3 leukemia sensitive MI-503 Preclinical Actionable In a preclinical study, MI-503 reduced progression and improved survival of a mouse leukemia model expressing KMT2A-MLLT3 (MLL-AF9) (PMID: 25817203). 25817203
KMT2A - MLLT3 acute myeloid leukemia not applicable N/A Guideline Prognostic KMT2A-MLLT3 fusions are associated with an intermediate prognosis in patients with non-APL acute myeloid leukemia (NCCN.org). detail...
KMT2A - MLLT3 acute myeloid leukemia sensitive GSK3203591 + MS023 Preclinical - Cell culture Actionable In a preclinical study, MS023 and GSK3203591 synergistically inhibited survival of murine KMT2A-MLLT3 (reported as MLL-AF9)-driven acute myeloid leukemia (AML) cells and human AML cell lines harboring KMT2A-MLLT3 in culture (PMID: 31408619). 31408619
KMT2A - MLLT3 acute myeloid leukemia sensitive E7107 + MS023 Preclinical - Cell culture Actionable In a preclinical study, MS023 and E7107 synergistically inhibited survival of murine KMT2A-MLLT3 (reported as MLL-AF9)-driven acute myeloid leukemia cells in culture, regardless of SRSF2 mutation status (PMID: 31408619). 31408619
KMT2A - MLLT3 acute myeloid leukemia sensitive E7107 + GSK3203591 Preclinical - Cell culture Actionable In a preclinical study, E7107 and GSK3203591 synergistically inhibited survival of murine KMT2A-MLLT3 (reported as MLL-AF9)-driven acute myeloid leukemia cells in culture, regardless of SRSF2 mutation status (PMID: 31408619). 31408619
KMT2A - MLLT3 acute myeloid leukemia predicted - sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KMT2A-MLLT3 was sensitive to treatment with CYC065 (Fadraciclib) in culture (PMID: 32645016). 32645016
KMT2A - MLLT3 acute myeloid leukemia sensitive Tretinoin Preclinical - Cell culture Actionable In a preclinical study, treatment with Tretinoin in acute myeloid leukemia cells harboring a KMT2A-MLLT3 fusion induced expression of myeloid differentiation markers, CD11b and PU.1, and resulted in growth inhibition, and in a murine cell model resulted in upregulation of Mac-1 and C/EBPalpha and growth inhibition in culture (PMID: 23063977). 23063977
KMT2A - MLLT3 acute myeloid leukemia sensitive Decitabine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, combination of Tretinoin and Dacogen (decitabine) in acute myeloid leukemia cells harboring KMT2A-MLLT3 resulted in significant growth inhibition, and greatly induced myeloid differentiation as indicated by CD11b and C/EBPalpha expression, and downregulation of c-Myc, and in a murine cell model, resulted in greater upregulation of C/EBPalpha and growth inhibition, and increased apoptosis compared to Tretinoin alone in culture (PMID: 23063977). 23063977
KMT2A - MLLT3 FLT3 exon 14 ins acute myeloid leukemia sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring a FLT3-ITD and KMT2A-MLLT3 was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating reduced cell viability, increased PARP cleavage, and decreased Mcl1 protein levels (PMID: 32645016). 32645016
KMT2A - MLLT3 NRAS G12D leukemia predicted - sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, expression of NRAS G12D in murine leukemia cells harboring KMT2A-MLLT3 resulted in increased sensitivity to treatment with PD-0325901 in culture (PMID: 33563661). 33563661
KMT2A - MLLT3 NRAS G12D leukemia sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, expression of NRAS G12D in murine leukemia cells harboring KMT2A-MLLT3 resulted in increased sensitivity to treatment with Mekinist (trametinib) in culture (PMID: 33563661). 33563661
KMT2A - SEPTIN6 acute myeloid leukemia sensitive I-BET151 + SGC0946 Preclinical - Patient cell culture Actionable In a preclinical study, I-BET151 and SGC0946 synergistically inhibited proliferation of patient-derived acute myeloid leukemia cells harboring KMT2A-SEPTIN6 in culture (PMID: 27294782). 27294782
KMT2A rearrange leukemia predicted - sensitive Doxorubicin + I-CBP112 Preclinical Actionable In a preclinical study, I-CBP112 sensitized leukemia cells harboring KMT2A fusions to Doxorubicin, leading to decreased cell growth in culture (PMID: 26552700). 26552700
KMT2A rearrange leukemia predicted - sensitive I-CBP112 + JQ1 Preclinical Actionable In a preclinical study, I-CBP112 sensitized leukemia cells harboring KMT2A fusions to JQ1, resulting in decreased cell growth in culture (PMID: 26552700). 26552700
KMT2A rearrange acute myeloid leukemia not applicable N/A Guideline Prognostic KMT2A rearrangements (t(v;11q23.3)) are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org). detail...
KMT2A rearrange acute myeloid leukemia not applicable N/A Clinical Study Prognostic In multiple clinical studies, KMT2A rearrangements, specifically partial tandem duplications, were associated with a poor overall survival in acute myeloid leukemia patients (PMID: 24487413, PMID: 22915647, PMID: 22417203, PMID: 21881046). 21881046 24487413 22417203 22915647
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Panobinostat Preclinical - Cell culture Actionable In a preclinical study, Farydak (panobinostat) enhanced the effects of Cytosar-U (cytarabine) in acute lymphoblastic leukemia cells harboring a KMT2A rearrangement in culture, resulting in cell death (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Mocetinostat Preclinical - Cell culture Actionable In a preclinical study, Mocetinostat (MGCD0103) enhanced the effects of Cytosar-U (cytarabine) in acute lymphoblastic leukemia cell lines harboring a KMT2A rearrangement in culture, resulting in cell death (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Dacinostat Preclinical - Cell culture Actionable In a preclinical study, Dacinostat (LAQ824) enhanced the effects of Cytosar-U (cytarabine) in acute lymphoblastic leukemia cell lines harboring a KMT2A rearrangement in culture, resulting in cell death (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Romidepsin Preclinical - Cell line xenograft Actionable In a preclinical study, Istodax (romidepsin) enhanced the effects of Cytosar-U (cytarabine) in acute lymphocytic leukemia cell lines harboring a KMT2A rearrangement in culture, and in cell line xenograft models, demonstrating decreased leukemic cells by 73% (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia decreased response Romidepsin Preclinical - Cell line xenograft Actionable In a preclinical study, Istodax (romidepsin) resulted in minimal activity in acute lymphocytic leukemia cell lines harboring a KMT2A rearrangement in culture, and in cell line xenograft models, demonstrating decreased leukemic cells by 16% (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine Preclinical - Cell line xenograft Actionable In a preclinical study, Cytosar-U (cytarabine) decreased leukemic cells by 66% in acute lymphocytic leukemia cell line xenograft models harboring a KMT2A rearrangement (PMID: 27443263). 27443263
KMT2A rearrange acute myeloid leukemia predicted - sensitive KO-539 Preclinical - Cell line xenograft Actionable In a preclinical study, KO-539 inhibited growth of KMT2A (MLL1)-rearranged acute myeloid leukemia cells in culture, and prolonged survival in cell-line xenograft models (AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A27). detail...
KMT2A rearrange acute leukemia predicted - sensitive Pinometostat Case Reports/Case Series Actionable In a Phase I trial, Pinometostat (EPZ-5676) treatment resulted in complete remission in 2 patients with KMT2A rearranged (both with t(11;19)) acute leukemia (PMID: 29724899; NCT01684150). 29724899
KMT2A rearrange childhood B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic KMT2A rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...
KMT2A rearrange acute myeloid leukemia sensitive CYC065 Preclinical - Cell line xenograft Actionable In a preclinical study, CYC065 (Fadraciclib) treatment resulted in decreased cell viability in an acute myeloid leukemia cell line harboring a KMT2A rearrangement in culture and inhibited tumor growth in a cell line xenograft model (PMID: 32645016). 32645016
KMT2A rearrange acute lymphoblastic leukemia predicted - sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, acute lymphoblastic leukemia cell lines harboring KMT2A rearrangements were sensitive to treatment with CYC065 (Fadraciclib) in culture (PMID: 32645016). 32645016
KMT2A rearrange B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic KMT2A rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...