Epigenetic changes accompany altered hemoglobin regulation in juvenile myelomonocytic leukemia

Elevated fetal hemoglobin (HbF) is a common observation in juvenile myelomonocytic leukemia (JMML) and an adverse prognostic factor. We previously reported that DNA hypermethylation of distinct target genes in JMML is also a negative prognostic factor and correlates with altered HbF expression. This led us to speculate that aberrant DNA methylation may be directly involved in the reexpression of HbF in JMML erythroid progenitors. We used mass spectrometry to measure CpG methylation of various target regions linked to hemoglobin regulation. Consistent with reexpression of gamma-globin, we found that the gamma-glo…