Stass S, Mirro J, Melvin S, Pui C H, Murphy S B, Williams D
Blood. 1984 Sep;64(3):701-6.
Conversions of leukemic cell lineage (lymphoid or myeloid) have been reported only rarely. Our review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic leukemia (ANLL), and one had converted from ANLL to ALL. Each child received lineage-specific multiagent chemotherapy when initially diagnosed, and all achieved a complete remission. After conversion, four patients readily achieved second remissions with treatment for the phenotype evident at lineage switch. Two patients with ANLL at conversion failed ALL-directed reinduction, while one of the two responded to high-dose cytarabine but died during bone marrow hypoplasia, emphasizing the importance of prompt recognition of lineage switch and selection of an appropriate plan of retreatment. Cytogenetic studies disclosed evidence of clonal selection in one patient and clonal stability in two. These findings indicate an unexpectedly high frequency of lineage switch in patients who relapse in the bone marrow after intensive chemotherapy. Although specific causative factors could not be identified, our observations suggest at least two general mechanisms for lineage switch in acute leukemia. In one, chemotherapy appears to eradicate the dominant clone present at diagnosis, permitting expansion of a secondary clone with a different phenotype. In the second, drug-induced changes in the original clone may either amplify or suppress differentiation programs so that phenotypic shift is possible.
白血病细胞系（淋巴系或髓系）的转化仅被罕见报道。我们对89例骨髓复发的儿童白血病的细胞化学和免疫表型特征进行回顾，发现6例患者（6.7%）出现了系别转换（淋巴系到髓系或相反）。5例初诊为急性淋巴细胞白血病（ALL）的患者转变为急性非淋巴细胞白血病（ANLL），1例从ANLL转变为ALL。每个患儿在初诊时均接受了针对系别的多药化疗，且均达到完全缓解。转换后，4例患者通过针对系别转换时明显的表型进行治疗，很容易地实现了第二次缓解。2例转换时为ANLL的患者在进行ALL导向的再诱导治疗时失败，而其中1例对大剂量阿糖胞苷有反应，但在骨髓抑制期死亡，这强调了及时识别系别转换并选择合适的再治疗方案的重要性。细胞遗传学研究发现1例患者有克隆选择的证据，2例有克隆稳定性。这些发现表明，在强化化疗后骨髓复发的患者中，系别转换的频率出乎意料地高。尽管无法确定具体的致病因素，但我们的观察结果提示急性白血病系别转换至少有两种一般机制。一种机制是，化疗似乎根除了诊断时存在的优势克隆，使具有不同表型的次要克隆得以扩增。另一种机制是，药物诱导的原始克隆变化可能会放大或抑制分化程序，从而使表型转变成为可能。
