Coexistence of Philadelphia chromosome in acute promyelocytic leukaemia: two rare cases, with a literature review

Background: Acute promyelocytic leukaemia (APL) is characterised by the t(15;17)/PML::RARA translocation and typically responds favourably to differentiating agents such as all-trans retinoic acid (ATRA). The coexistence of APL with the Philadelphia chromosome (t(9;22)/BCR::ABL1), a hallmark of chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL), is extremely rare and carries uncertain prognostic and therapeutic implications. Case description: We describe two cases where these studies confirmed APL with t(15;17)(q22;q21), in addition to t(9;22)(q34;q11), consistent with dual cytogenetic abnormalities. The patient was initiated on induction therapy with ATRA in combination with idarubicin, resulting in rapid haematologic remission by day 15, with normalisation of blood counts and significant clinical improvement. Conclusion: These cases highlight the diagnostic and therapeutic challenges posed by APL with concurrent BCR::ABL1 rearrangement. While the PML::RARA clone responded robustly to ATRA-based therapy, the persistence of BCR::ABL1 warrants consideration of tyrosine kinase inhibitor (TKI) therapy and close molecular monitoring. Our report contributes to the limited body of literature on this rare dual-driver leukaemia and underscores the need for individualised, biology-driven management strategies.