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 failing 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.

Archambeault, S., Flores, N. J., Yoshimi, A., Kratz, C. P., Reising, M., Fischer, A., Noellke, P., Locatelli, F., Sedlacek, P., Flotho, C., Zecca, M., Emanuel, P. D., Castleberry, R. P., Niemeyer, C. M., Bader, P., Loh, M. L., Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia, <<BLOOD>>, 2008; 111 (8): 1124-1127. [doi:10.1182/blood-2007-06-093302] [https://hdl.handle.net/10807/258445]

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

Locatelli, Franco;
2008

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 failing 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.
2008
Inglese
Archambeault, S., Flores, N. J., Yoshimi, A., Kratz, C. P., Reising, M., Fischer, A., Noellke, P., Locatelli, F., Sedlacek, P., Flotho, C., Zecca, M., Emanuel, P. D., Castleberry, R. P., Niemeyer, C. M., Bader, P., Loh, M. L., Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia, <<BLOOD>>, 2008; 111 (8): 1124-1127. [doi:10.1182/blood-2007-06-093302] [https://hdl.handle.net/10807/258445]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/258445
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 31
  • ???jsp.display-item.citation.isi??? 28
social impact