Detection of BCR-ABL kinase domain mutations in CD34 + cells from newly diagnosed chronic phase CML patients and their association with imatinib resistance

摘要: ABSTRACT BCR-ABL kinase domain (KD) mutations, the most common cause of imatinib resistance, are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) patients. Recent studies indicate pre-existing mutations (PEMs) can be a higher percentage CML patients using CD34 + stem/progenitor cells, and these may correlate with resistance. We investigated KD stem cells from 100 CP-CML by multiplex ASO-PCR sequencing products at time diagnosis. PEMs were 32/100 included F311L, M351T, T315I. After median follow-up 30 months (range 8–48), all exhibited Of 68 without PEMs, 24 developed Mutations 21 sequencing. All 32 had same mutations. In imatinib-resistant we Y253F, T315I Y253F responded to dose escalation. conclusion, substantial number when