Expansion of the hematopoietic stem cell compartment is necessary but not sufficient for gain-of-function mutant p53 R248Q to accelerate lymphomagenesis

Dear Editor,

The importance of hematopoietic stem cells (HSCs) in the development of leukemias and lymphomas derived from mature lymphocytic cells is increasingly being recognized.¹ Genetic and epigenetic changes occurring in the HSC compartment may either be maintained in differentiated cells and/or cooperate with other mutations that are acquired by differentiating cell populations. For example, HSCs isolated from CLL (chronic lymphocytic leukemia) patients show aberrancy in their subsequent differentiation characteristics, including skewed B-cell differentiation and generation of oligoclonal B-cell populations.² Moreover, patients with T-cell lymphomas containing TET2 mutations were shown to carry this mutation already in early hematopoietic progenitors.³ These examples illustrate that some initiating events in lymphomagenesis may occur very early in hematopoietic differentiation.

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