Mantle cell lymphoma and the evidence of an immature lymphoid component

Mantle cell lymphoma (MCL) is a rare B cell malignancy. The classical MCL subtype is positive for translocation t(11;14), SOX11 expression, and characterized as a mature B cell neoplasm. While it is evident that differentiated B lymphocytes comprise the principal constituent of this malignancy, the possibility of an immature component involving immature progenitor, precursor, or even multipotent stem cells exists. It is now known that many hematologic malignancies are preceded by clonal hematopoiesis or a premalignant phase, which may involve early progenitors, and that such mutations can persist following treatment. Here, we thematically review and discuss the existing evidence pointing to an immature contribution of MCL in some cases. With the ongoing transition towards comprehensive genomic profiling, it is now possible to thoroughly investigate whether an immature genomic profile accompanies the morphologically lymphoblastic appearance of the blastoid subtype. This profile may include the expression of genes related to the pre-B cell receptor or genes required for the development and differentiation of B cell progenitors and precursors, such as transcription factor, SOX4, and the terminal transferase, DNTT. Research into the likely immature component of MCL is motivated by the relevance in treatment strategies because such cells potentially constitute a reservoir with increased resistance. In conclusion, further evidence on the concept, and definition, of lymphoma progenitors, precursors, or stem cell involvement in MCL is highly warranted.