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The Etiology of Chronic Lymphocytic Leukemia: Another Look at the Relationship Between B1 cells and CLL

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease of unknown etiological origin. CLL is the only B cell malignancy where a characteristic chromosomal translocation is not involved in cancer initiation. Therefore, the cause of tumorigenesis in CLL patients and the type of cell that is transformed are two questions that have intrigued researchers for decades. However, evidence suggests the CLL cell may be derived from B-1 cells. These B-1 cells, thought to develop during neonatal maturation as a link between innate and adaptive immunity, share multiple phenotypic and genetic patterns with CLL cases. These include signaling molecules sensitivity and expression patterns, B-cell receptor (BCR) specificity, and a unique immune-modulatory phenotype. Through understanding the biological relevance of B-1 cells in immune development and regulation, we may further understand the molecular mechanisms underlying the complexity of CLL. With this understanding, we can provide more optimal care to patients based on their unique diagnosis and pathologic disease course. In this review, based on our current understanding of CLL cells and B1 cells we hypothesize that CLL cells are originated from B1 cells. Following are some of our rationale in deriving this hypothesis.