Hematopoiesis in patients with mature B-cell malignancies is deregulated even in patients with undetectable bone marrow involvement

摘要

Mature B-cell malignancies represent the most common types of hematologic tumors. Despite this, little information is available on the composition and function of hematopoiesis in patients with these malignancies. Hematopoietic stem and progenitor cells (HSPCs) might be influenced by at least three key factors: 1. HSPC-intrinsic mutations (that might predispose subjects to the development of these malignancies), 2. Direct or indirect impact of malignant lymphocytes present in the bone marrow (BM) or extramedullary tissue, and 3. Age-related changes.~(~(1)~(5)) The aim of the study herein was to analyze HSPC content in patients with thus far untreated mature B-cell malignancies.We first confirmed the age-related changes observed by Kuranda et al. in our cohort of 22 control samples.~(~(6)) While the absolute numbers of hematopoietic stem cells (HSCs) did not change, we observed a negative correlation of their relative numbers with increasing age (Figure 1A,C). The absolute, but not relative numbers of multipotent progenitors (MPPs) positively correlated with age (Figure 1A,C). The most statistically significant change was observed in the compartment of multilymphoid progenitors (MLPs), where both the absolute and relative frequencies positively correlated with age (Figure 1A,C). Both the absolute and relative numbers of pro-B cells were significantly lower in the control samples of the elderly (Figure 1A,C). In addition to the age-related changes, we have recently demonstrated that healthy Caucasians have significantly increased proportions of BM-derived pro-B cells compared to Asians.~(~(7)) To avoid any potential age- or race-related biases in HSPC frequencies, the control cohort used in this study comprised BM samples obtained from age-matched healthy Caucasians (all patients were Caucasians as well). The flow cytometry gating strategy is explained in detail in the Online Supplementary Materials and Methods .