Immunology and Rheumatology Department, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Argentina.
Am J Hematol. 2012 Sep;87(9):890-7. doi: 10.1002/ajh.23266. Epub 2012 Jun 8.
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.
虽然很少见，但在治疗急性白血病（AL）期间，淋巴细胞和髓系细胞之间可能会发生转换。正确的诊断依赖于免疫表型确认谱系转换，并证明尽管表型发生变化，但相同的细胞遗传学/分子改变仍然存在。在总共 1482 名儿科 AL 患者中，我们报告了 9 例谱系转换（0.6%），其中 7 例从淋巴细胞（4 例前 B，2 例前 B，1 例常见）到髓系单核细胞，2 例从髓系（双谱系，以髓系为主）到前 B。8 名患者为婴儿。形态学提示转换，并在治疗开始后中位数 15 天（范围：8 天-6 个月）确认。值得注意的是，在 5 例病例中，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。在 7 例病例中检测到 11q23/MLL 基因异常。治疗方案为 ALL（2 例）、Interfant-99（5 例）和 AML（2 例）方案。尽管根据新的谱系改变化疗，但所有患者均死亡。我们的发现支持谱系转换与 MLL 基因改变有关，涉及共同的淋巴样 B-髓样前体。应设计新的治疗方法来解决这些罕见病例。讨论了可能涉及的机制。
