在费城阴性骨髓增生性肿瘤中，母细胞转化是一种罕见但众所周知的事件，与不良预后相关。由骨髓增生性肿瘤演变而来的继发性急性髓系白血病的特征是具有与新发疾病不同的一组独特的细胞遗传学和分子特征。 t(8;21) (q22;q22.1); RUNX1::RUNX1T1 是新发急性髓系白血病中最常见的细胞遗传学异常之一，在骨髓增殖后肿瘤急性髓系白血病中很少观察到。在此报告一例由JAK2突变原发性血小板增多症演变而来的t(8;21)继发性急性髓性白血病。患者为74岁日本女性，因血小板增多症（血小板1046 × 109/L）转诊。 。骨髓细胞增多，巨核细胞增多。染色体分析显示核型正常，基因检测显示 JAK2 V617F 突变。她被诊断患有原发性血小板增多症。口服羟基脲可以很好地控制血小板增多症；初次诊断 ET 2 年后，她出现白细胞增多（白细胞 14.0 × 109/L，其中原始细胞为 82%）、贫血（血红蛋白 91 g/L）和血小板减少症（血小板 24 × 109/L）。骨髓细胞丰富，充满了 80% 带有 Auer 棒的髓过氧化物酶阳性母细胞。染色体分析显示 t(8;21) (q22;q22.1) 和流式细胞术显示 CD 13、19、34 和 56 呈阳性。分子分析显示 RUNX1::RUNX1T1 嵌合转录物和杂合 JAK2 V617F 突变共存白血病急变。她被诊断患有继发性急性髓系白血病，t(8;21)(q22;q22.1)； RUNX1::RUNX1T1 由原发性血小板增多症演变而来。她接受了维奈托克和阿扎胞苷的联合化疗。第一个治疗周期后，外周血中原始细胞消失，骨髓中原始细胞减少至 1.4%。化疗后，RUNX1::RUNX1T1嵌合转录本消失，而外周白细胞中JAK2 V617F突变仍然存在。据我们所知，本病例是第一例在获得t(8;21)之前发生JAK2突变的病例。我们的结果表明 t(8;21); RUNX1::RUNX1T1 可以作为 JAK2 突变骨髓增殖性肿瘤进展中的晚期事件而产生。该病例呈现出与 t(8;21) 急性髓系白血病相关的典型形态学和免疫表型特征。© 2024。作者。

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.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.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.© 2024. The Author(s).