Higher Level of Peripheral Blood CD34 Positive Cells Presented with Unfavorable Prognosis in Intermediate-Low Risk Acute Promyelocytic Leukemia

Zhang, Cuiling; Dong, Haibo; Lin, Yipeng; Xu, Peipei; Zhou, Rong-Fu; Zeng, Hui

doi:10.1007/s12288-019-01232-4

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…In mice, most steady-state circulating PB HSPCs show no long-term repopulating potential 25 , often fail to re-enter the BM 18,26,27 , or change phenotype after their egress 27 . In humans, increased frequencies of CD34 + cells in PB are observed in many hematopoietic diseases, notably in sickle cell anemia and b-thalassemia, and in cardiovascular, autoimmune and rheumatological conditions 21,[28][29][30][31][32][33][34] , but with very few studies providing further resolution of CD34 + subsets. It has long been assumed that steady-state PB HSPC composition mirrors that of the BM but no baseline steady-state circulating HSPC composition has been reported to date.…”

Section: Introductionmentioning

confidence: 99%

Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans

Mende¹,

Bastos

Santoro

et al. 2022

Blood

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Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although non-mobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remains untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB and mobilized PB (mPB) to BM using single-cell RNA-seq and/or functional assays. We uncover HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we find no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state, but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary stem cells/multipotent progenitors (HSC/MPPs) from spleen, PB and mPB share a common transcriptional signature and increased abundance of lineage-primed subsets compared to BM. Third, healthy PB HSPCs display a unique bias towards erythroid-megakaryocytic differentiation. At HSC/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSC/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age, in essential thrombocythemia and in beta-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are non-proliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction.

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