The bone marrow microenvironment and its impact in acute and chronic B cell malignancies

The bone marrow (BM) hosts normal hematopoiesis by providing the cellular and molecular environment necessary for hematopoietic stem cell maintenance, expansion, and differentiation into the various hematopoietic lineages. This highly organized factory requires cross talk between hematopoietic and stromal elements in distinct microanatomical sites (niches), promoting the expansion of normal hematopoietic elements and the deletion of defective and potentially harmful cells [1]. The neoplastic cells from patients with lymphoid malignancies take advantage of the BM microenvironment by parasitizing niches that normally are restricted to hematopoietic progenitors [2]. Interactions with the marrow microenvironment contribute to malignant B cell growth and drug resistance, leading to a gradual replacement of normal hematopoiesis. In lymphoid malignancies, the BM also is a common site for residual disease and relapses after conventional therapies [3]. Therefore, there is growing interest in understanding the biology of the BM microenvironment. Over the last two decades, there has been substantial progress in identifying key cellular and molecular players in cross talk between malignant lymphocytes and the marrow microenvironment. In this chapter, we will highlight established pathways and current therapeutic approaches to target the microenvironment in acute and chronic B cell malignancies.