IN MULTIPLE-MYELOMA, CLONOTYPIC B-LYMPHOCYTES ARE DETECTABLE AMONG CD19(+) PERIPHERAL-BLOOD CELLS EXPRESSING CD38, CD56, AND MONOTYPIC IG LIGHT-CHAIN

IN MULTIPLE-MYELOMA, CLONOTYPIC B-LYMPHOCYTES ARE DETECTABLE AMONG CD19(+) PERIPHERAL-BLOOD CELLS EXPRESSING CD38, CD56, AND MONOTYPIC IG LIGHT-CHAIN
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DOI:
10.1182/blood.v85.2.436.bloodjournal852436
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发表时间:
1995-01-15
期刊:
影响因子:
20.3
通讯作者:
PILARSKI, LM
PILARSKI, LM
中科院分区:
医学1区
文献类型:
--
作者:
BERGSAGEL, PL;SMITH, AM;PILARSKI, LM

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多发性骨髓瘤(MM)的特征在于骨髓(BM)的浆细胞浸润。然而,已在血液中检测到晚期单型B细胞。本研究分析了临床治疗对152例MM患者的752份血液样本中晚期CD 19(+)B细胞的影响。MM患者的循环CD 19(+)细胞是正常供体的2 - 8倍。使用聚合酶链反应分析IG重链(IgH)基因重排表明,对于化疗期间或复发期间分析的患者,CD 19(+)群体包括与BM浆细胞中检测到的克隆型CDR 3区相同的细胞。它们也是单型的,如通过其IG κ或λ轻链的细胞质或表面表达所定义的。轻链限制与BM浆细胞相同。在1- 2年的观察期内,个体患者血液中存在的B细胞数量存在相当大的差异;该数量与血清单克隆IG浓度无关。单克隆血液CD 19(+)细胞不会被分析的任何化疗方案消除,并且在短暂缓解期间保持在高水平。处于疾病进展期或复发期的患者的B细胞数量显著高于短暂缓解期或未治疗患者。在血液B细胞数量接近正常的时期,表型上它们的质量是高度异常的,具有物理和表型异质性。大多数B细胞表达晚期B或前浆细胞特征性的CD 45 R 0、高密度的CD 38和CD 56。CD 38(hi)血B细胞呈周期性分布。我们的结论是,骨髓瘤患者血液中的单克隆B细胞包括可能导致复发的克隆型细胞的耐药储库。(C)1995年,美国血液学会。
Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the hone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical treatment on late stage CD19(+) B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD19(+) cells as do normal donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates that the CD19(+) population includes cells sharing the same clonotypic CDR3 region as is detected in the BM plasma cells, for patients analyzed during chemotherapy or in relapse. They are also monotypic as defined by their cytoplasmic or surface expression of Ig kappa- or lambda light chain. The light chain restriction is the same as that of the BM plasma cells. Individual patients observed over 1- to 2-year periods exhibit considerable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal Ig. The monoclonal blood CD19(+) cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during transient remissions. Patients in the progressive phase of disease or in relapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the quantity of blood B cells approaches normal, phenotypically their quality is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38(hi) blood B cells had a cyclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse. (C) 1995 by The American Society of Hematology.