Gupta Aditya Kumar, Meena Jagdish Prasad, Chopra Anita, Tanwar Pranay, Seth Rachna
Division of Pediatric Oncology, Department of Pediatrics, All India Institute of Medical Sciences New Delhi 110029, India.
Laboratory Oncology Unit, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi 110029, India.
Am J Blood Res. 2021 Feb 15;11(1):1-21. eCollection 2021.
Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myelodysplastic/myeloproliferative neoplasm overlap disease. JMML is associated with mutations in the RAS pathway genes resulting in the myeloid progenitors being sensitive to granulocyte monocyte colony-stimulating factor (GM-CSF). Karyotype abnormalities and additional epigenetic alterations can also be found in JMML. Neurofibromatosis and Noonan's syndrome have a predisposition for JMML. In a few patients, the genes (, and ) are mutated at the germline and this usually results in a transient myeloproliferative disorder with a good prognosis. JMML with somatic mutation behaves aggressively. JMML presents with cytopenias and leukemic infiltration into organs. The laboratory findings include hyperleukocytosis, monocytosis, increased hemoglobin-F levels, and circulating myeloid precursors. The blast cells in the peripheral blood/bone-marrow aspirate are less than 20% and the absence of the BCR-ABL translocation helps to differentiate from chronic myeloid leukemia. JMML should be differentiated from immunodeficiencies, viral infections, intrauterine infections, hemophagolymphohistiocytosis, other myeloproliferative disorders, and leukemias. Chemotherapy is employed as a bridge to HSCT, except in few with less aggressive disease, in which chemotherapy alone can result in long term remission. Azacitidine has shown promise as a single agent to stabilize the disease. The prognosis of JMML is poor with about 50% of patients surviving after an allogeneic hematopoietic stem cell transplant (HSCT). Allogeneic HSCT is the only known cure for JMML to date. Myeloablative conditioning is most commonly used with graft versus host disease (GVHD) prophylaxis tailored to the aggressiveness of the disease. Relapses are common even after HSCT and a second HSCT can salvage a third of these patients. Novel options in the treatment of JMML e.g., hypomethylating agents, MEK inhibitors, JAK inhibitors, tyrosine kinase inhibitors, etc. are being explored.
青少年粒单核细胞白血病（JMML）是一种罕见的儿童骨髓增生异常/骨髓增殖性肿瘤重叠疾病。JMML与RAS通路基因突变有关，导致髓系祖细胞对粒细胞-单核细胞集落刺激因子（GM-CSF）敏感。核型异常和其他表观遗传改变也可在JMML中发现。神经纤维瘤病和努南综合征易患JMML。在少数患者中，基因（、和）在种系中发生突变，这通常导致预后良好的短暂性骨髓增殖性疾病。伴有体细胞突变的JMML表现侵袭性。JMML表现为血细胞减少和白血病浸润器官。实验室检查结果包括白细胞增多、单核细胞增多、血红蛋白F水平升高和循环髓系前体细胞。外周血/骨髓穿刺涂片中的原始细胞少于20%，且不存在BCR-ABL易位有助于与慢性粒细胞白血病相鉴别。JMML应与免疫缺陷、病毒感染、宫内感染、噬血细胞性淋巴组织细胞增生症、其他骨髓增殖性疾病和白血病相鉴别。化疗用作异基因造血干细胞移植（HSCT）的过渡治疗，少数病情不那么侵袭性的患者除外，这些患者单独化疗即可获得长期缓解。阿扎胞苷作为单一药物已显示出稳定病情的前景。JMML的预后较差，约50%的患者在接受异基因造血干细胞移植（HSCT）后存活。异基因HSCT是迄今为止已知的唯一可治愈JMML的方法。清髓性预处理最常使用，移植物抗宿主病（GVHD）预防措施根据疾病的侵袭性进行调整。即使在HSCT后复发也很常见，二次HSCT可挽救其中三分之一的患者。正在探索治疗JMML的新方法，例如去甲基化药物、MEK抑制剂、JAK抑制剂、酪氨酸激酶抑制剂等。
