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Molecular Genetics: B-cell prolymphocytic leukemia (B-PLL) usually has a complex karyotype. In a large study, the most frequent abnormalities were associated with the MYC gene resulting in its overexpression. MYC translocations involving IGH, IGK, or IGL loci were found in 62% of cases. MYC gains or amplification were seen in another 15% of cases - MYC translocation and MYC gains being mutually exclusive.

Deletion of 17p13 or TP53 mutations (50% of cases), and 13q14 deletions (25% of cases) are additional cytogenetic alterations in B-PLL. 17p13 deletion or TP53 mutations are associated with poor outcome due to primary resistance to first-line chemotherapy drugs.

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