Anastasi J, Musvee T, Roulston D, Domer P H, Larson R A, Vardiman J W
Department of Pathology, University of Chicago Medical Center, IL 60637, USA.
Leukemia. 1998 Feb;12(2):233-7. doi: 10.1038/sj.leu.2400900.
The results of polymerase chain reaction (PCR) analysis after transplantation for chronic myelogenous leukemia (CML) are difficult to interpret clinically. Positive findings for BCR/ABL can be seen not only in patients who go on to relapse but also in patients who, after years of follow-up, remain in complete remission. The cause for the lack of concordance between PCR findings and relapse is not clear. We identified two patients with CML who had rare pseudo-Gaucher cells in their bone marrow aspirate specimens prior to, and at 1, and 6 or 12 months following syngeneic or allogeneic hematopoietic transplantation. After the transplant, the patients obtained clinical remission and were shown to be cytogenetically normal and to have germline MBCR in blood or bone marrow by Southern analysis. One patient was PCR-positive for BCR/ABL in the marrow at 12 months. In order to determine whether the pseudo-Gaucher histiocytes were BCR/ABL-positive, we used fluorescence in situ hybridization and probes for MBCR and ABL and analyzed Wright-stained smears to correlate molecular cytogenetic findings with cell type. On three aspirate smears from each patient (at 6 or 12 months post-transplant), all of the pseudo-Gaucher cells studied (10/10 in one patient and 12/12 in the other) showed the fusion for BCR/ABL. Other cells analyzed randomly (erythroid precursors, granulocytes and rare monocytes, lymphocytes and plasma cells) did not. Our cases provide the first proof that pseudo-Gaucher cells carry the BCR/ABL fusion. Furthermore, they illustrate that these cells can be found in the marrow for up to 12 months following transplantation. Our results permit speculation that pseudo-Gaucher cells or other long-lived histocytes may be one cause of persistent PCR positivity after transplantation that is not predictive of disease relapse.
慢性粒细胞白血病（CML）移植后的聚合酶链反应（PCR）分析结果在临床上难以解读。BCR/ABL呈阳性不仅可见于后续复发的患者，也可见于经过数年随访仍处于完全缓解状态的患者。PCR结果与复发之间缺乏一致性的原因尚不清楚。我们鉴定了两名CML患者，在同基因或异基因造血移植前、移植后1个月、6个月或12个月时，其骨髓穿刺标本中存在罕见的假戈谢细胞。移植后，患者获得临床缓解，Southern分析显示其细胞遗传学正常，血液或骨髓中存在种系MBCR。一名患者在12个月时骨髓中BCR/ABL的PCR检测呈阳性。为了确定假戈谢组织细胞是否为BCR/ABL阳性，我们使用荧光原位杂交技术以及针对MBCR和ABL的探针，并分析瑞氏染色涂片，以将分子细胞遗传学结果与细胞类型相关联。在每位患者的三张穿刺涂片上（移植后6个月或12个月），所有研究的假戈谢细胞（一名患者为10/10，另一名患者为12/12）均显示出BCR/ABL融合。随机分析的其他细胞（红系前体细胞、粒细胞、罕见的单核细胞、淋巴细胞和浆细胞）则未显示。我们的病例首次证明假戈谢细胞携带BCR/ABL融合。此外，这些病例表明，移植后长达12个月均可在骨髓中发现这些细胞。我们的结果提示，假戈谢细胞或其他长寿组织细胞可能是移植后PCR持续阳性但不预示疾病复发的原因之一。
