Fitzgerald P H, Morris C M
Cytogenetic and Molecular Oncology Unit, Christchurch Hospital, New Zealand.
Cancer Genet Cytogenet. 1989 Oct 1;42(1):9-25. doi: 10.1016/0165-4608(89)90003-4.
The Philadelphia (Ph) chromosome usually results from the t(9;22), which causes the physical association of the BCR1 and ABL genes and their function as a single new gene. This precise genomic mutation probably has a significant role in the development of leukemia in humans, but that leukemia may take several forms: chronic myeloid leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia, and essential thrombocythemia; CML also transforms to a lymphoid or myeloid acute phase. Two models are considered with regard to determinants of this variable hematologic expression of BCR-ABL. The first is variation in the breakpoint site of BCR1. Two breakpoint sites, M-BCR and m-BCR, are known, and their occurrence shows a nonrandom association with the different forms of leukemia. The precise position of the breakpoint within M-BCR may also be important. The second model concerns the role of other genes in determining the leukemic form shown by BCR-ABL. Results are reviewed of a patient who entered blast crisis CML and whose leukemic clones involved ten genetic loci with known leukemic associations. Many of these were probably genetic variants that allowed leukemic proliferations following the initiation of blast crisis. The multiplicity of these genes may obscure the prime determinant of blast crisis, which is unknown at the present time.
费城（Ph）染色体通常源于t(9;22)，它导致BCR1和ABL基因发生物理关联，并作为一个单一的新基因发挥作用。这种精确的基因组突变可能在人类白血病的发生发展中起重要作用，但白血病可能有几种形式：慢性髓性白血病（CML）、急性髓性白血病、急性淋巴细胞白血病和原发性血小板增多症；CML也会转变为淋巴细胞或髓细胞急性期。关于BCR-ABL这种可变血液学表现的决定因素，有两种模型被考虑。第一种是BCR1断点位点的变异。已知有两个断点位点，即M-BCR和m-BCR，它们的出现与不同形式的白血病呈现非随机关联。M-BCR内断点的确切位置可能也很重要。第二种模型涉及其他基因在决定BCR-ABL所表现出的白血病形式中的作用。本文回顾了一名进入CML急变期的患者的结果，其白血病克隆涉及十个与白血病相关的已知基因位点。其中许多可能是基因变异，在急变期开始后允许白血病增殖。这些基因的多样性可能掩盖了急变期的主要决定因素，而目前该因素尚不清楚。
