背景:Blast转化是费城阴性骨髓增殖性肿瘤中罕见但公认的不良预后事件。从骨髓增殖性肿瘤演变而来的继发性急性骨髓性白血病的特征是一组独特的细胞遗传学和分子特征,与从头疾病不同。t(8;21)(q22;q22.1);RUNX1::RUNX1T1,从头急性髓细胞性白血病中最常见的细胞遗传学异常之一,在骨髓增殖性肿瘤后急性髓细胞性白血病中很少观察到。在这里,我们报告了一例继发性急性髓细胞性白血病,其t(8;21)是从JAK2突变的原发性血小板增多症演变而来的。
方法:患者是一名74岁的日本女性,因血小板增多(血小板1046×109/L)而转诊。随着巨核细胞的增加,骨髓细胞增多。染色体分析显示正常核型,遗传测试显示JAK2V617F突变。她被诊断为原发性血小板增多症。通过口服羟基脲,血小板增多得到了很好的控制;在最初诊断为ET后2年,她出现白细胞增多症(白细胞14.0×109/L,占母细胞的82%),贫血(血红蛋白91g/L),血小板减少(血小板24×109/L)。骨髓细胞过多,充满了80%的髓过氧化物酶阳性胚细胞,带有Auer棒。染色体分析显示t(8;21)(q22;q22.1),流式细胞术显示CD13、19、34和56呈阳性。分子分析显示白血病母细胞中RUNX1::RUNX1T1嵌合转录物和杂合JAK2V617F突变共存。她被诊断为继发性急性髓性白血病,患有t(8;21)(q22;q22.1);RUNX1::RUNX1T1从原发性血小板增多症演变而来。她接受了维奈托克和氮杂胞苷的联合化疗。在第一个周期的治疗之后,母细胞从外周血中消失,骨髓中降至1.4%。化疗后,RUNX1::RUNX1T1嵌合转录物消失,而外周白细胞中仍存在JAK2V617F突变。
结论:据我们所知,本病例是第一个在获得t(8;21)之前具有JAK2突变的病例。我们的结果表明t(8;21);RUNX1::RUNX1T1可以作为JAK2突变的骨髓增殖性肿瘤进展的晚期事件产生。该病例具有与t(8;21)急性髓细胞性白血病相关的典型形态学和免疫表型特征。
BACKGROUND: Blast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia.
METHODS: The patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes.
CONCLUSIONS: To our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia.