1 research outputs found
Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia
Juvenile myelomonocytic leukemia is an
aggressive and frequently lethal myeloproliferative disorder of childhood. Somatic mutations in NRAS, KRAS, or
PTPN11 occur in 60% of cases. Monitoring disease status is difficult because of
the lack of characteristic leukemic blasts
at diagnosis. We designed a fluorescently
based, allele-specific polymerase chain
reaction assay called TaqMAMA to detect
the most common RAS or PTPN11 mutations. We analyzed peripheral blood
and/or bone marrow of 25 patients for
levels of mutant alleles over time. Analysis of pre–hematopoietic stem-cell transplantation, samples revealed a broad distribution of the quantity of the mutant
alleles. After hematopoietic stem-cell
transplantation, the level of the mutant
allele rose rapidly in patients who relapsed and correlated well with falling
donor chimerism. Simultaneously analyzed peripheral blood and bone marrow
samples demonstrate that blood can be
monitored for residual disease. Importantly, these assays provide a sensitive
strategy to evaluate molecular responses
to new therapeutic strategies