Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene KMT2A AFF1
Variant KMT2A - AFF1
Impact List fusion
Protein Effect gain of function
Gene Variant Descriptions KMT2A-AFF1 (also referred to as MLL-AF4) results from the fusion of KMT2A and AFF1, resulting in repression of CDKN1B transcription, which eventually leads to leukemogenesis (PMID: 20194896, PMID: 16169901).
Associated Drug Resistance
Category Variants Paths

KMT2A mutant KMT2A rearrange KMT2A fusion KMT2A - AFF1

KMT2A mutant KMT2A act mut KMT2A - AFF1

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 Vesanoid (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 Vesanoid (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 leukemia predicted - sensitive DSP-5336 Preclinical - Pdx & cell culture Actionable In a preclinical study, DSP-5336 treatment inhibited growth of a leukemia cell line harboring KMT2A-AFF1 (reported as MLL-AF4) in culture, led to antitumor activity in a cell line xenograft model, and resulted in remission and improved survival in a patient-derived xenograft (PDX) model (Blood (2021) 138 (Supplement 1): 3339). detail...