When multiple myeloma and chronic lymphocytic leukemia appear in the same patient, they do not derive from the same B-cell but rather develop independently from separate B-cells, according to an investigation by Jana Wobst, PhD, and colleagues from the MLL Munich Leukemia Laboratory in Germany.
The results were published in a letter to the journal Leukemia.
While both diseases originate from B-lineage cells at different differentiation stages—monoclonal plasma cells for MM and mature naïve or memory B-cells for CLL—their simultaneous occurrence is rare.
By analyzing the B-cell receptors and genetic mutations of 495 patients, Dr. Wobst and colleagues sought to determine whether these co-occurring neoplasms derived from a common progenitor or represented independent oncogenic events. The study used advanced diagnostic techniques, including whole-genome sequencing, to look for shared genetic fingerprints between the two conditions.
The study concluded that MM and CLL (or its precursor, monoclonal B-cell lymphocytosis) are almost exclusively clonally unrelated, developing independently from separate B-cells in patients where both malignancies coexist.
Through IGH rearrangement analysis (primarily via the LymphoTrack assay), 17 out of 18 informative cases demonstrated distinct rearrangements, indicating separate developmental pathways. Beyond BCR analysis, the study looked at somatic variants across a 66-gene panel, finding that 26 of 27 patients had entirely distinct mutation profiles for each disease.
While one patient did show a shared genetic marker suggesting a common, very early ancestor, the actual cancer clones remained distinct and unrelated in their later development. These findings suggest that the co-occurrence of these cancers is likely a coincidence of age or shared environmental risk factors rather than one cancer turning into the other.
“Our findings, supported by published data, strongly suggest that cases with co-occurring MM and CLL arising from the same B cell, if any, are exceptionally rare,” the authors wrote. “Future research might uncover biomarkers in cases where MM and CLL coexist that could serve as predictors for risk factors developing secondary malignancies with the ultimate goal of identifying optimized treatment strategies targeting shared pathways.”
