Acute Myeloid Leukemia With Philadelphia Chromosome and Complex Karyotype: A Diagnostic Dilemma

Acute myeloid leukemia (AML) is a hematological malignancy driven by the clonal expansion of immature myeloid cells, with cytogenetic findings playing a defining role in both its diagnosis and risk stratification. The Philadelphia chromosome, generated by the t(9;22)(q34;q11.2) translocation and the resulting BCR-ABL1 fusion gene, is a well-known driver of chronic myeloid leukemia (CML). Its occurrence in AML, however, is uncommon and carries distinct diagnostic and therapeutic implications that are not always straightforward to navigate. We report a 47-year-old male patient who came to us with a 10-day history of fever, hip pain, and back pain. Blood tests showed anemia and thrombocytopenia, with 49% blasts on peripheral smear. Bone marrow biopsy confirmed acute leukemia with 63% blasts. Cytogenetic studies revealed t(9;22) along with a remarkably complex karyotype, with trisomies of eight chromosomes and tetrasomies of three others. The patient received high-dose cytarabine over three cycles, developed febrile neutropenia requiring amikacin, and was subsequently started on imatinib 400 mg in view of the BCR-ABL1 positivity. He has remained clinically stable at six months of follow-up. To our knowledge, finding Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) alongside such a degree of additional chromosomal numerical gains is exceptionally rare. What makes this case worth reporting is the convergence of three issues that each present their own challenges: establishing a diagnosis of de novo AML rather than CML in blast crisis, managing an already aggressive disease made more so by a complex karyotype, and deciding on the role of tyrosine kinase inhibitors in a disease setting where their use is not yet standardized. Detailed cytogenetic workup proved critical in navigating all three.