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Allografting

Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT

Abstract

Monitoring of minimal residual disease (MRD) after allogeneic (allo)-SCT for myelofibrosis (MF) allows recognizing the depth of remission and thus guides application of appropriate therapeutic interventions. MPL W515L/K mutations, which are detected in 5–10% of JAK2V617F-negative patients, may be useful for this purpose. Using a highly sensitive quantitative PCR method, we tested 90 patients with MF who underwent allo-SCT for the presence of MPL W515L/K mutations. Two patients with primary MF were found to harbor MPLW515L while no patient was positive for MPLW515K mutation. Both patients were JAK2V617F negative and cleared the mutation rapidly after allo-SCT and remained negative for a median follow-up of 19 months. The results of molecular monitoring correlated well with other remission parameters such as normalization of peripheral blood counts and morphology and complete donor chimerism. We conclude that MPLW515L can be cleared after allo-SCT and hence may be used as an MRD marker in a proportion of JAK2V617F-negative MF patients.

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Acknowledgements

We are grateful to Ronan Chaligne and Jean-Pierre Le Couedic for providing the sequences of primers and probes for designing MPL-PCR assay. We also thank Alessandro M Vannucchi for providing the plasmids for mutated and wild-type MPL. HA is a recipient of an EBMT-AMGEN fellowship 2008.

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Correspondence to N Kröger.

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Alchalby, H., Badbaran, A., Bock, O. et al. Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT. Bone Marrow Transplant 45, 1404–1407 (2010). https://doi.org/10.1038/bmt.2009.367

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