TY - JOUR
T1 - Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia
AU - Archambeault, Sophie
AU - Flores, Nikki J.
AU - Yoshimi, Ayami
AU - Kratz, Christian P.
AU - Reising, Miriam
AU - Fischer, Alexandra
AU - Noellke, Peter
AU - Locatelli, Franco
AU - Sedlacek, Petr
AU - Flotho, Christian
AU - Zecca, Marco
AU - Emanuel, Peter D.
AU - Castleberry, Robert P.
AU - Niemeyer, Charlotte M.
AU - Bader, Peter
AU - Loh, Mignon L.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2007-06-093302
DO - 10.1182/blood-2007-06-093302
M3 - Article
C2 - 18000165
AN - SCOPUS:38949143672
VL - 111
SP - 1124
EP - 1127
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -