Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia

Sophie Archambeault, Nikki J. Flores, Ayami Yoshimi, Christian P. Kratz, Miriam Reising, Alexandra Fischer, Peter Noellke, Franco Locatelli, Petr Sedlacek, Christian Flotho, Marco Zecca, Peter D. Emanuel, Robert P. Castleberry, Charlotte M. Niemeyer, Peter Bader, Mignon L. Loh

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1124-1127
Number of pages4
JournalBlood
Volume111
Issue number3
DOIs
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Hematology

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