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移植外周血 CD34+ 细胞上的 CXCR4 表达:与多发性骨髓瘤患者自体移植后植入的关系。

CXCR4 expression on transplanted peripheral blood CD34+ cells: relationship to engraftment after autologous transplantation in a cohort of multiple myeloma patients.

机构信息

Bone Marrow Transplant Laboratory, Department of Clinical Haematology, St. George Hospital, Kogarah, Sydney, NSW, 2217, Australia.

出版信息

Ann Hematol. 2011 May;90(5):547-55. doi: 10.1007/s00277-010-1097-8. Epub 2010 Oct 19.

Abstract

Expression of the chemokine receptor CXCR4 by haematopoietic stem cells (HSCs) is believed to influence the process of these cells 'homing' back to the bone marrow post-transplantation, in response to the stromal cell-derived factor-1 gradient, followed by engraftment. The primary aim of this retrospective study was to compare reinfused CD34(+) cell dose, assessed from the fresh collection, with the post-thaw viable (v) CD34(+) and vCD34/CXCR4(+) dual positive cell dose as predictors of haematopoietic recovery in multiple myeloma patients undergoing autologous stem cell transplantation. Cryopreserved samples from stem cell collections of 27 myeloma patients were analysed for CD34 and CXCR4 expression and times to haematological engraftment measured. Dosage of transplanted vCD34(+) cells was on average 79% of the original calculation from the fresh collection bag (range 29-98%). The median percentage of vCD34+ cells co-expressing CXCR4 was 37% (3.7-97%). Surface expression of CXCR4 by thawed vCD34(+) cells was closely correlated to complementary DNA levels. The median dose of CD34/CXCR4(+) cells in the autografts was 1.2 × 10(6)/kg (0.2-3.0 × 10(6)/kg) compared with 3.3 × 10(6)/kg for transplanted vCD34(+) cells (1.2-5.5 × 10(6)/kg). Both CD34 and vCD34 doses correlated with neutrophil engraftment (p < 0.005) although vCD34/CXCR4(+) dose did not. However, patients given a higher dose of CD34/CXCR4(+) cells (≥1.75 × 10(6)/kg) showed a faster time to platelet recovery (p < 0.05) than those given a lower dose (≤0.42 × 10(6)/kg). These results warrant further study of CD34/CXCR4 expression by mobilised HSCs and the relationship to platelet recovery post-transplantation on a larger cohort of patients.

摘要

造血干细胞(HSCs)表达趋化因子受体 CXCR4 被认为会影响这些细胞在移植后“归巢”回到骨髓的过程,以响应基质细胞衍生因子-1 梯度,然后进行植入。这项回顾性研究的主要目的是比较从新鲜采集物中评估的再输注 CD34(+)细胞剂量与解冻后存活(v)CD34(+)和 vCD34/CXCR4(+)双阳性细胞剂量,以预测多发性骨髓瘤患者自体干细胞移植后的造血恢复。对 27 例骨髓瘤患者的干细胞采集物的冷冻样本进行了 CD34 和 CXCR4 表达分析,并测量了血液学植入的时间。移植的 vCD34(+)细胞的剂量平均为新鲜采集袋原始计算值的 79%(范围为 29-98%)。vCD34+细胞共表达 CXCR4 的中位数百分比为 37%(3.7-97%)。解冻的 vCD34(+)细胞表面表达的 CXCR4 与 cDNA 水平密切相关。自体移植物中 CD34/CXCR4(+)细胞的中位数剂量为 1.2×10(6)/kg(0.2-3.0×10(6)/kg),而移植的 vCD34(+)细胞剂量为 3.3×10(6)/kg(1.2-5.5×10(6)/kg)。CD34 和 vCD34 剂量均与中性粒细胞植入相关(p<0.005),尽管 vCD34/CXCR4(+)剂量不相关。然而,给予较高剂量 CD34/CXCR4(+)细胞(≥1.75×10(6)/kg)的患者血小板恢复更快(p<0.05),而给予较低剂量(≤0.42×10(6)/kg)的患者则较慢。这些结果需要进一步研究动员的 HSCs 中 CD34/CXCR4 的表达及其与移植后血小板恢复的关系,以更大的患者队列进行研究。

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