Juvenile myelomonocytic leukemia: a report from the 2nd International JMML Symposium

Abstract

Juvenile myelomonocytic leukemia (JMML) is an aggressive childhood myeloproliferative disorder characterized by the overproduction of myelomonocytic cells. JMML incidence approaches 1.2/million persons in the United States (Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995). Although rare, JMML is innately informative as the molecular genetics of this disease implicates hyperactive Ras as an essential initiating event. Given that Ras is one of the most frequently mutated oncogenes in human cancer, findings from this disease are applicable to more genetically diverse and complex adult leukemias. The JMML Foundation (www.jmmlfoundation.org) was founded by parent advocates dedicated to finding a cure for this disease. They work to bring investigators together in a collaborative manner. This article summarizes key presentations from The Second International JMML Symposium, on 7-8 December 2007 in Atlanta, GA. A list of all participants is in Supplementary Table.

Figure 1

Schematic diagram of A) normal hematopoietic differentiation; B) accumulation of undifferentiated myeloblasts representing acute myeloid leukemia; and C) increased production of monocytic cells along the full spectrum of differentiation, including blast forms, promonocytes, monocytes, and macrophages, as observed in juvenile myelomonocytic leukemia. HSC = hematopoietic stem cell; CMP = common myeloid progenitor; GMP = granulocyte monocyte progenitor.

Figure 2

Schematic diagram showing ligand-stimulated Ras activation, the Ras-Erk pathway, and the gene mutations found to date contributing to the neuro-cardio-facio-cutaneous congenital disorders and JMML. NL/MGCL – Noonan-like/multiple giant cell lesion; CFC – Cardia-facio-cutaneous; JMML – juvenile myelomonocytic leukemia.