CML with T315I gatekeeper mutation in the BCR-ABL1 kinase domain — resistant to all 1st/2...

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

ID	`RF-CML-T315I-MUTATION`
Type	Red flag
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	`DIS-CML`
Sources	`SRC-ELN-CML-2020` `SRC-NCCN-MPN-2025`

Red Flag Origin

Definition	CML with T315I gatekeeper mutation in the BCR-ABL1 kinase domain — resistant to all 1st/2nd-gen TKIs; requires ponatinib or asciminib (STAMP)
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-CML-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "bcr_abl_t315i",
      "value": true
    },
    {
      "finding": "kinase_domain_mutation",
      "value": "T315I"
    }
  ],
  "type": "biomarker"
}

Notes

T315I emergence on imatinib / 2nd-gen TKI mandates switch to ponatinib (full-dose 45 mg → response-adjusted to 15 mg per OPTIC) or asciminib STAMP (response rates ~50% in T315I-positive). Both NOT registered in Ukraine — major access barrier. AlloHCT remains alternative for fit patients without ponatinib/asciminib access. Mandatory kinase-domain resistance mutation screening at TKI failure or suboptimal response per ELN 2020 milestones. STUB — requires clinical co-lead signoff.

Used By

Algorithms

ALGO-CML-1L - ALGO-CML-1L
ALGO-CML-2L - ALGO-CML-2L

Indications

IND-CML-1L-2GEN-TKI - IND-CML-1L-2GEN-TKI
IND-CML-1L-IMATINIB - IND-CML-1L-IMATINIB
IND-CML-2L-PONATINIB-T315I - IND-CML-2L-PONATINIB-T315I
IND-CML-3L-ASCIMINIB - IND-CML-3L-ASCIMINIB