Anastasi J, Feng J, Le Beau M M, Larson R A, Rowley J D, Vardiman J W
Department of Pathology, University of Chicago, IL, USA.
Leukemia. 1995 Apr;9(4):628-33.
Chronic myelogenous leukemia (CML) is a stem cell disorder which progresses from a chronic phase (CP) to an accelerated phase (AP), and/or a blast phase (BP) of myeloid (M) or lymphoid (L) phenotype. This progression is frequently preceded or accompanied by recurring secondary chromosomal abnormalities which are believed to play a role in the transformation. In order to investigate the relationship between the secondary change and the development of BP, we undertook a study using fluorescence in situ hybridization to determine in which cells the secondary abnormalities were present. We observed that in one case of L-BP, the secondary change (trisomy 8) appeared to be in a subclone that was different from the blast cells, as it was absent from the lymphoblasts but present in differentiating erythroid, monocytic and granulocytic cells. In two cases, the secondary change (trisomy 8, extra Ph) probably occurred prior to an acute transforming event as it was present in CP or AP predominantly in differentiated granulocytic or monocytic cells. In one case of M-BP, the secondary change (trisomy 8) probably occurred after the acute transformation, as it appeared in only a subset of the blasts. Lastly, in four cases of L-BP, the secondary change (monosomy 7, extra Ph or hyperdiploidy) was closely associated with the BP as it was present in all of the blasts. The findings indicate that some secondary abnormalities may be directly related to the development of BP and may provide clues to the identity of genes responsible for the acute phase transition. Other abnormalities occurring before, or after the acute transformation or in a different subclone from the acute phase blasts, may be more important for denoting genomic instability than for helping to understand the mechanism of blast transformation.
慢性粒细胞白血病（CML）是一种干细胞疾病，它从慢性期（CP）进展为加速期（AP），和/或髓系（M）或淋巴系（L）表型的急变期（BP）。这种进展通常之前或伴随有反复出现的继发性染色体异常，这些异常被认为在转化过程中起作用。为了研究继发性改变与急变期发展之间 的关系，我们进行了一项研究，使用荧光原位杂交来确定继发性异常存在于哪些细胞中。我们观察到，在一例L-BP中，继发性改变（三体8）似乎存在于一个与原始细胞不同的亚克隆中，因为在淋巴母细胞中不存在，但存在于分化的红系、单核系和粒系细胞中。在两例中，继发性改变（三体8，额外的费城染色体）可能发生在急性转化事件之前，因为它主要存在于CP或AP期的分化粒系或单核系细胞中。在一例M-BP中，继发性改变（三体8）可能发生在急性转化之后，因为它仅出现在一部分原始细胞中；最后，在四例L-BP中，继发性改变（单体7，额外的费城染色体或超二倍体）与急变期密切相关，因为它存在于所有原始细胞中。这些发现表明，一些继发性异常可能与急变期的发展直接相关，并可能为负责急性期转变的基因的身份提供线索。其他在急性转化之前、之后或存在于与急性期原始细胞不同的亚克隆中的异常，可能对于表明基因组不稳定性比帮助理解原始细胞转化机制更为重要。
