Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations

• Published in: Blood Vol. 109; no. 12; pp. 5477 - 5480
• Main Authors: Matsuda, Kazuyuki, Shimada, Akira, Yoshida, Nao, Ogawa, Atsushi, Watanabe, Akihiro, Yajima, Shuhei, Iizuka, Susumu, Koike, Kazutoshi, Yanai, Fumio, Kawasaki, Keiichiro, Yanagimachi, Masakatsu, Kikuchi, Akira, Ohtsuka, Yoshitoshi, Hidaka, Eiko, Yamauchi, Kazuyoshi, Tanaka, Miyuki, Yanagisawa, Ryu, Nakazawa, Yozo, Shiohara, Masaaki, Manabe, Atsushi, Kojima, Seiji, Koike, Kenichi
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-06-2007; The Americain Society of Hematology
• Subjects: Amino Acid Substitution; Biological and medical sciences; Blood Cells - pathology; Female; Granulocyte Precursor Cells; Hematologic and hematopoietic diseases; Humans; Infant; Leukemia, Myelomonocytic, Chronic - diagnosis; Leukemia, Myelomonocytic, Chronic - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Mutation - physiology; Neoplasm Regression, Spontaneous - genetics; ras Proteins - genetics; ras Proteins - physiology; Human; Spontaneous; Malignant hemopathy; Myelodysplastic syndrome; Myeloproliferative syndrome; C-Onc gene; Genetics; Remission; Juvenile myelomonocytic leukemia; Mutation; Ras gene; Child; Protooncogene
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-09-046649

Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoietic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMML with specific RAS mutations may have spontaneously improving disease.