关键词: RAS基因；　自身免疫；　白细胞增殖性疾病；　免疫缺陷综合征

Abstract: Objective　To explore the clinical process and genetic variation characteristics of RAS-associated autoimmune leukoproliferative disease (RALD) evolving into severe juvenile myelomonocytic leukemia (JMML). Methods　The clinical data of RALD evolving into JMML and KRAS gene mutation in a child were retrospectively analyzed, and the related literature was reviewed. Results　A male child presented with pale complexion and hepatosplenomegaly at 2 months of age, with a peripheral leukocyte count at 17.56×109/L, a monocyte ratio of 5.8% and a heterozygous deletion in α4.2 gene. Subsequently, the patient suffered repeated fever, aggravated anemia and continuing hepatosplenomegaly. Laboratory data showed fluctuated leukocyte count at (16.4~58)×109/L, increased monocyte ratio at (21.4%~36%), decreased platelet count at (50~110)×109/L and positive result of Coomb's test. There was no obvious abnormality in bone marrow smear at 4 months of age. After treatment, the condition improved and the drug was stopped. At the age of 2 years, the child presented with persistent high fever again. Laboratory data showed that HbF was at 28.9%. The chest CT showed that the patient had suspicious pulmonary fungal infection, pericardial effusion and bilateral axillary multiple enlarged lymph nodes. Bone marrow morphology suggested an infectious myelogram. Flow cytometry showed about 1.2% myeloid primordial cells and 7.6% monocytes. Bone marrow fluorescence in situ hybridization (FISH) reported no leukemia-associated fusion gene. The heterozygous missense variation, c.37G>T (p.Gly13Cys), was detected in exon 2 of KRAS gene. At age of 2 years and 4 months, the child developed fever again, with 51% of peripheral blood immature cells. He was finally diagnosed as JMML. Conclusions　RALD and JMML are continuous processes of different clinical phenotypes and disease progressions resulting from a range of genetic and epigenetic events. It is necessary to closely monitor the changes in condition of RALD patients for early diagnosis and treatment.

Key words: RAS gene;　autoimmunity;　leukoproliferative disorder;　immunodeficiency syndrome