A Rare Case of Myelofibrosis Progressing to BCR-ABL1-Positive Chronic Myeloid Leukemia With Discordant Molecular Testing

Myelofibrosis is a chronic myeloproliferative neoplasm (CMN) characterized by bone marrow fibrosis, splenomegaly, cytopenias, or cytoses, and a propensity for transformation into acute myeloid leukemia (AML). Transformation of myelofibrosis into chronic myeloid leukemia (CML), however, is extremely rare and poorly understood. CML is typically defined by the presence of the BCR-ABL1 fusion gene, a product of the Philadelphia chromosome t(9;22)(q34;q11), which leads to constitutive activation of a tyrosine kinase that drives leukemogenesis. This molecular abnormality is considered pathognomonic for CML and is routinely identified through techniques such as fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). While the transformation from myelofibrosis to CML is unusual, this case report illustrates an unusual transformation of myelofibrosis to CML, marked by the emergence of a BCR-ABL1-positive clone detectable by fluorescence in situ hybridization (FISH) but not by polymerase chain reaction (PCR). It underscores the importance of using multiple complementary molecular diagnostic techniques when evaluating disease progression in myeloproliferative neoplasms. Early recognition of such atypical transformations is essential, as it can open the door to targeted therapies that may significantly alter the patient's prognosis and clinical trajectory.