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Cancer Health Center

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Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Juvenile Myelomonocytic Leukemia


Morphologically, the peripheral blood picture in this disease shows leukocytosis, anemia, and frequently, thrombocytopenia.[6,7,8,9,14,15] The median reported white blood cell count varies from 25 × 109 /L to 35 × 109 /L. In 5% to 10% of children with JMML, however, it is greater than 100 × 109 /L. The leukocytosis is comprised of neutrophils, promyelocytes, myelocytes, and monocytes. Blasts, including promonocytes, usually account for less than 5% of the white blood cells and always for less than 20%. Nucleated red blood cells are seen frequently. Thrombocytopenia is typical and may be severe.[6,7,8,9,14,15] Bone marrow findings include the following:[6,7,9,14,15]

  • Hypercellularity with granulocytic proliferation.
  • Hypercellularity with erythroid precursors (in some patients).
  • Monocytes comprising 5% to 10% of marrow cells (30% or more in some patients).
  • Minimal dysplasia.
  • Reduced numbers of megakaryocytes.

A distinctive characteristic of JMML leukemia cells is their spontaneous proliferation in vitro without the addition of exogenous stimuli, an ability that results from the leukemia cells being hypersensitive to GM-CSF.[16,17] No Philadelphia chromosome or BCR/ABL fusion gene exists. Although cytogenetic abnormalities, including monosomy 7, occur in 30% to 40% of patients, none is specific for JMML.[6,15,18] In JMML associated with NF1, loss of the normal NF1 allele is common, and loss of heterozygosity for NF1 has been observed in some patients with JMML who lack the NF1 phenotype.[18] This genetic alteration results in a loss of neurofibromin, a protein that is involved in the regulation of the ras family of oncogenes.[18] Point mutations in ras have been reported to occur in the leukemic cells of 20% of patients with JMML.[6,19]

The median survival times for JMML vary from approximately 10 months to more than 4 years, depending partly on the type of therapy chosen.[8,9,20] Prognosis is related to age at the time of diagnosis. The prognosis is better in children younger than 1 year at the time of diagnosis. Children older than 2 years at the time of diagnosis have a much worse prognosis.[6,8] A low platelet count and a high Hb F level have been associated with a worse prognosis.[9,14] Approximately 10% to 20% of cases may evolve to acute leukemia.[8,9]

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