Aberrations of MYC are a common event in B-cell prolymphocytic leukemia.

B-cell prolymphocytic leukemia (B-PLL) remains a controversial entity, and its molecular pathogenesis is largely unknown. Patients are older, typically having marked lymphocytosis and splenomegaly in the absence of lymphadenopathy. It is defined as a mature B-cell leukemia with more than 55% circulating prolymphocytes. Leukemic mantle cell lymphoma and chronic lymphocytic leukemia in prolymphocytic transformation must be excluded. Case archives were retrospectively reviewed for B-PLL in patients without a previous diagnosis of chronic lymphocytic leukemia or other B-cell neoplasm. We identified six cases of B-PLL with available cytogenetic data, five of which showed evidence of aberrations in MYC. Three cases showed additional signals for the MYC gene by fluorescence in situ hybridization (FISH), and two cases demonstrated t(8;14)MYC/IGH by karyotyping or FISH. High levels of MYC protein expression were detected in all cases tested with MYC aberrations. These results suggest that deregulation of MYC plays an important role in the pathogenesis of B-PLL and expands the spectrum of B-cell neoplasms associated with aberrations of MYC.