Lasho Terra, Patnaik Mrinal M
Division of Hematology, Mayo Clinic Rochester, USA.
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Best Pract Res Clin Haematol. 2020 Jun;33(2):101171. doi: 10.1016/j.beha.2020.101171. Epub 2020 Apr 29.
Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic/myeloproliferative neoplasm overlap syndrome with sustained peripheral blood monocytosis, aggressive features, and poor outcomes. In >90% of cases JMML is driven by germline or somatic mutations involving the canonical RAS pathway (PTPN11, NRAS, CBL, KRAS and NF1), with somatic mutations/alterations in RAS pathway genes (second hit), SETBP1, ASXL1 and JAK3 resulting in disease progression. While spontaneous regression has been seen in germline PTPN11 and CBL mutant JMML, in most patients, allogeneic stem cell transplant is the only curative modality. JMML shares several phenotypic features with its adult counterpart proliferative, chronic myelomonocytic leukemia (pCMML). pCMML largely occurs due to RAS pathway mutations that occur in the context of age related clonal hematopoiesis (TET2, SRSF2, ASXL1), while JMML is a bona fide RASopathy, with additional somatic mutations, including in epigenetic regulators genes resulting in disease progression.
青少年骨髓单核细胞白血病（JMML）是一种儿童骨髓增生异常/骨髓增殖性肿瘤重叠综合征，具有持续性外周血单核细胞增多、侵袭性特征和不良预后。在90%以上的病例中，JMML由涉及经典RAS通路（PTPN11、NRAS、CBL、KRAS和NF1）的种系或体细胞突变驱动，RAS通路基因（二次打击）、SETBP1、ASXL1和JAK3中的体细胞突变/改变导致疾病进展。虽然在种系PTPN11和CBL突变的JMML中可见自发缓解，但在大多数患者中，异基因干细胞移植是唯一的治愈方式。JMML与其成人对应物增殖性慢性粒单核细胞白血病（pCMML）具有一些共同的表型特征。pCMML主要由于在与年龄相关的克隆性造血（TET2、SRSF2、ASXL1）背景下发生的RAS通路突变而发生，而JMML是一种真正的RAS病，具有额外的体细胞突变，包括表观遗传调节基因中的突变，导致疾病进展。
