Lineage switch in childhood acute leukemia: An unusual event with poor outcome
Lineage switch in childhood acute leukemia: An unusual event with poor outcome
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DOI：
10.1002/ajh.23266
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发表时间：
2012-09-01
影响因子：
12.8
通讯作者：
Felice, Maria S.
中科院分区：
文献类型：
--
作者：
Rossi, Jorge G.;Bernasconi, Andrea R.;Felice, Maria S.
虽然很少，但在急性白血病（AL）治疗期间可能会发生淋巴和骨髓谱系之间的转换。正确的诊断依赖于谱系转换的免疫表型确认和尽管表型改变但仍然存在相同的细胞遗传学/分子改变的证明。在总共1，482例AL儿科患者中，我们报告了9例谱系转换（0.6%），7例从淋巴（4例Pro-B，2例Pre-B，1例普通）到骨髓单核细胞，2例从骨髓（双线，以骨髓为主）到Pro-B。8例患者为婴儿。通过形态学提示转换，并在治疗开始后中位15天（范围：8天-6个月）内确认。值得注意的是，在5个病例中，转换发生在第15天之前。通过细胞遗传学、RT-PCR/Ig-TCR重排研究评估所有患者克隆异常的稳定性。11 q23/MLL基因缺失7例。治疗方案为ALL（2例患者）、Interfant-99（5例患者）和AML（2例患者）方案。尽管根据新的谱系改变了化疗，但所有患者都死亡。我们的研究结果支持与MLL基因的改变和一个共同的淋巴B-髓样前体的参与谱系开关的关联。应该设计新的治疗方法来解决这些罕见的病例。可能的机制进行了讨论。Am.血液学杂志，2012. (c)2012 Wiley Periodicals，Inc.
Although rarely, switches between lymphoid and myeloid lineages may occur during treatment of acute leukemias (AL). Correct diagnosis relies upon confirmation by immunophenotyping of the lineage conversion and certification that the same cytogenetic/molecular alterations remain despite the phenotypic changes. From a total of 1,482 AL pediatric patients, we report nine cases of lineage conversion (0.6%), seven from lymphoid (four Pro-B, two Pre-B, one Common) to myelo-monocytic, and two from myeloid (bilineal, with myeloid predominance) to Pro-B. Eight patients were infants. Switches were suggested by morphology and confirmed with a median of 15 days (range: 8 days-6 months) from initiation of therapy. Of note, in five cases switches occurred before day 15. Stability of the clonal abnormalities was assessed by cytogenetic, RT-PCR/Ig-TCR rearrangement studies in all patients. Abnormalities in 11q23/MLL gene were detected in seven cases. Treatment schedules were ALL (two pts), Interfant-99 (five pts) and AML (two pts) protocols. Despite changing chemotherapy according to the new lineage, all patients died. Our findings support the association of lineage switches with MLL gene alterations and the involvement of a common lymphoid B-myeloid precursor. New therapies should be designed to address these rare cases. Possible mechanisms implicated are discussed. Am. J. Hematol., 2012. (c) 2012 Wiley Periodicals, Inc.