Fialkow P J, Martin P J, Najfeld V, Penfold G K, Jacobson R J, Hansen J A
Blood. 1981 Jul;58(1):158-63.
To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B-lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A-type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.
为了研究费城染色体（Ph1）与慢性粒细胞白血病发病机制的关系，从一名X染色体连锁酶葡萄糖-6-磷酸脱氢酶杂合的Ph1阳性白血病患者身上建立了多个B淋巴细胞系。在正常组织中发现A、B两种类型的酶比例为1:1，但从该患者获得的63个Ph1阴性B淋巴细胞系中有45个（71%）仅显示出在Ph1阳性白血病克隆中发现的单一葡萄糖-6-磷酸脱氢酶（B型）。此外，33个可分析的B型酶细胞系中有8个存在染色体畸变，而14个A型葡萄糖-6-磷酸脱氢酶细胞系中无一例出现染色体畸变。这些结果为以下观点提供了证据：异常克隆的一些细胞不表达Ph1异常。因此，获得Ph1可能不是该疾病的充分病因。Ph1阳性慢性粒细胞白血病的发病机制可能至少涉及两个步骤，一个导致多能造血干细胞克隆的异常增殖，另一个在这些祖细胞的后代中诱导Ph1的产生。
