Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mod Pathol. 2017 Jul;30(7):940-951. doi: 10.1038/modpathol.2017.19. Epub 2017 Mar 24.
Classical Philadelphia chromosome-negative myeloproliferative neoplasms are a group of closely related myeloid disorders with different histologic features and clinical presentations at an early stage, but all later develop into a similar fibrotic stage with variable risk of acute transformation. The significance of 3q26.2/EVI1 rearrangement has been well recognized in acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. However, the clinical importance of 3q26.2/EVI1 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is unknown. Here we reported 15 patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms showing 3q26.2 rearrangement, including inv(3)(q21q26.2) (n=6), t(3;21)(q26.2;q22)(n=4), t(3;3)(q21;q26.2)(n=3), inv(3)(q13.3q26.2)(n=1), and t(3;12)(q26.2;p13)(n=1). In addition to 3q26.2 rearrangement, 9 of 15 cases had other concurrent karyotypical abnormalities, including -7/7q- and -5/5q-. There were 8 men and 7 women with a median age of 59 years (range, 35-79 years) at initial diagnosis of myeloproliferative neoplasms: 8 patients had primary myelofibrosis, 4 had polycythemia vera, and 3 had essential thrombocythemia. JAK2 V617F mutation was detected in 8/14 patients, including 4/4 with polycythemia vera. The median interval from the initial diagnosis of myeloproliferative neoplasms to the detection of 3q26.2 rearrangement was 44 months (range, 1-219 months). At time of emergence of 3q26.2 rearrangement, 11 patients were in blast phase and 2 patients had increased blasts (6-19%). Dyspoiesis, predominantly in megakaryocytes, were detected in all patients with adequate specimens at time of 3q26.2 rearrangement. Following 3q26.2 rearrangement, 12 patients received chemotherapy, but none of them achieved complete remission. Of 14 patients with follow-up information, all died with a median overall survival time of only 3 months (range 0-14 months) after the emergence of 3q26.2 rearrangement. In summary, 3q26.2 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is associated with other concurrent cytogenetic abnormalities, a rapid disease progression and blast transformation, a poor response to chemotherapy and a dismal prognosis.
经典费城染色体阴性骨髓增殖性肿瘤是一组密切相关的髓系疾病，在早期具有不同的组织学特征和临床表现，但所有疾病后期都会发展为类似的纤维化阶段，具有不同的急性转化风险。3q26.2/EVI1 重排的意义在急性髓系白血病、骨髓增生异常综合征和慢性髓系白血病中已得到充分认识。然而，3q26.2/EVI1 重排在经典费城染色体阴性骨髓增殖性肿瘤中的临床意义尚不清楚。在这里，我们报告了 15 例经典费城染色体阴性骨髓增殖性肿瘤患者存在 3q26.2 重排，包括 inv(3)(q21q26.2)(n=6)、t(3;21)(q26.2;q22)(n=4)、t(3;3)(q21;q26.2)(n=3)、inv(3)(q13.3q26.2)(n=1)和 t(3;12)(q26.2;p13)(n=1)。除了 3q26.2 重排外，15 例中有 9 例存在其他并发核型异常，包括-7/7q-和-5/5q-。初诊时年龄中位数为 59 岁（范围为 35-79 岁），其中 8 例为原发性骨髓纤维化，4 例为真性红细胞增多症，3 例为原发性血小板增多症。14 例患者中有 8 例检测到 JAK2 V617F 突变，其中包括 4 例真性红细胞增多症患者。从骨髓增殖性肿瘤初诊到检测到 3q26.2 重排的中位间隔时间为 44 个月（范围为 1-219 个月）。在出现 3q26.2 重排时，11 例患者处于白血病期，2 例患者有增加的白血病细胞（6-19%）。在所有有足够标本的患者中，均检测到造血细胞发育不良，主要为巨核细胞。出现 3q26.2 重排后，12 例患者接受了化疗，但均未达到完全缓解。在有随访信息的 14 例患者中，所有患者在出现 3q26.2 重排后中位总生存期仅为 3 个月（范围为 0-14 个月），均死亡。综上所述，经典费城染色体阴性骨髓增殖性肿瘤中 3q26.2 重排与其他并发细胞遗传学异常、疾病快速进展和白血病转化、对化疗反应差和预后不良相关。
