Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
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 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 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 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
|
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 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
|
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
|
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
|
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 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
|
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 + 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
|
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
|
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...
|
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 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
|