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|Variant||KMT2A - AFF4|
|Protein Effect||gain of function|
|Gene Variant Descriptions||KMT2A-AFF4 (also referred to as MLL-AF5Q31) results from the fusion of KMT2A and AFF4 which leads to Ras-dependent activation of Elk1 (PMID: 20362031), increased expression of HOXA9, and cell transformation in culture (PMID: 20153263). KMT2A-AFF4 has been identified in acute lymphoblastic leukemia (PMID: 10588740, PMID: 12759932).|
|Associated Drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|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||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||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||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|
|Molecular Profile||Protein Effect||Treatment Approaches|
|KMT2A - AFF4||gain of function|