KMT2A rearrangement (MLL fusion at 11q23) in AML — ~5-10% prevalence in adult AML; ELN-20...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-AML-KMT2A-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-30 \| pending_clinical_signoff
Diseases	`DIS-AML`
Sources	`SRC-ELN-AML-2022` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	KMT2A rearrangement (MLL fusion at 11q23) in AML — ~5-10% prevalence in adult AML; ELN-2022 adverse-risk classifier. Revumenib (menin inhibitor; AUGMENT-101 phase 1/2) FDA-approved Nov 2024 for relapsed/ refractory KMT2A-rearranged acute leukemia after ≥1 prior line (ORR ~63%, CR/CRh ~23%). Ziftomenib alternative menin inhibitor in late-phase trials. Common partners: AF9 (t(9;11)) and AF4 (t(4;11)).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-AML-1L, ALGO-AML-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "kmt2a_rearrangement",
      "value": true
    },
    {
      "finding": "kmt2a_fusion",
      "value": true
    },
    {
      "finding": "mll_rearrangement",
      "value": true
    },
    {
      "finding": "mll_fusion",
      "value": true
    },
    {
      "finding": "kmt2a_status",
      "value": "rearranged"
    },
    {
      "finding": "karyotype_11q23",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Detection: karyotype + FISH break-apart probe at diagnosis; RT-PCR or RNA-NGS for fusion partner identification. Differentiation syndrome on revumenib (~16%) — monitor for fever, dyspnea, weight gain, effusions; treat with dexamethasone + hold revumenib until resolution. QTc prolongation requires baseline + serial ECG with K+/Mg++ correction. AlloHCT bridge for fit responders — revumenib alone NOT curative. Algorithm wiring deferred — IND-AML-2L-KMT2A- REVUMENIB created but not yet routed by ALGO-AML-2L (would require step-restructure, out of chunk scope). MDT review during chunk rollout. STUB — requires clinical co-lead signoff.

Used By

Indications

IND-AML-2L-KMT2A-REVUMENIB - IND-AML-2L-KMT2A-REVUMENIB