Lemoli R M
Istituto di Ematologia L. & A. Seràgnoli, Università di Bologna, Italia.
Haematologica. 1993 Nov-Dec;78(6):393-400.
Chronic myeloid leukemia (CML) is a clonal disorder arising from the hematopoietic stem cell, characterized by the Philadelphia chromosome (Ph) and, at the molecular level, by fusion of the BCR (breakpoint cluster region) gene and the c-ABL gene. The hallmark of CML is represented by a marked increase in the number of leukemic progenitors, as well as more mature cells, in the bone marrow (BM) and peripheral blood (PB). Despite expansion of the leukemic clone, normal Ph-negative stem cells have been demonstrated to survive in CML. Early observations of partial, but transient, restoration of Ph-negative hematopoiesis after high-dose chemotherapy have recently been extended by the use of myeloablative regimens followed by autografting with marrow or blood-derived stem cells. Moreover, treatment of early-stage CML patients with the biologic response modifier alpha-interferon (alpha-IFN) has led to the re-emergence of normal progenitor cells. Concurrently, "in-vitro" studies have reported that cultures of CML marrow in the presence of a stromal feeder-layer resulted in depletion of Ph-positive cells and predominance of Ph-negative hematopoietic precursors. Based on the assumption that normal and malignant stem cells may coexist in CML, several studies have recently been directed toward the characterization and "in-vitro" selection of benign progenitors within CML hematopoiesis. The results of those studies demonstrated that normal precursors can be phenotypically and functionally identified in the BM or PB of Ph-positive CML patients. These cells are included in the earliest identifiable hematopoietic cell compartment. Normal cells do not bear cell surface lymphoid or myeloid-lineage antigens, express high levels of the CD34 antigen, and fail to express the HLA-DR antigen. Furthermore, they possess a great capacity for adhering to marrow stroma. This cell population represents only a small minority of hematopoietic progenitors, but it retains many of the properties associated with putative hematopoietic stem cells. Thus, purification of a population of benign hematopoietic precursors that could be used for autologous bone marrow transplantation (ABMT) may be feasible in CML patients.
慢性髓性白血病（CML）是一种起源于造血干细胞的克隆性疾病，其特征为费城染色体（Ph），在分子水平上则是BCR（断裂点簇集区）基因与c-ABL基因融合。CML的标志是骨髓（BM）和外周血（PB）中白血病祖细胞以及更成熟细胞的数量显著增加。尽管白血病克隆有所扩增，但已证实正常的Ph阴性干细胞在CML中能够存活。早期关于高剂量化疗后Ph阴性造血功能部分但短暂恢复的观察，最近通过采用清髓方案并随后进行骨髓或血源干细胞自体移植得到了扩展。此外，用生物反应调节剂α-干扰素（α-IFN）治疗早期CML患者已导致正常祖细胞重新出现。同时，“体外”研究报告称，在基质饲养层存在的情况下培养CML骨髓会导致Ph阳性细胞减少，Ph阴性造血前体细胞占优势。基于正常和恶性干细胞可能在CML中共存的假设，最近有几项研究致力于对CML造血过程中的良性祖细胞进行表征和“体外”选择。这些研究结果表明，正常前体细胞可以在Ph阳性CML患者的BM或PB中通过表型和功能进行鉴定。这些细胞包含在最早可识别的造血细胞区室中。正常细胞不携带细胞表面淋巴或髓系谱系抗原，表达高水平的CD34抗原，且不表达HLA-DR抗原。此外，它们具有很强的黏附于骨髓基质的能力。这群细胞仅占造血祖细胞的一小部分，但保留了许多与假定造血干细胞相关的特性。因此，纯化可用于自体骨髓移植（ABMT）的良性造血前体细胞群体在CML患者中可能是可行的。
