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.

Allogeneic Stem Cell Transplantation for Myelofibrosis in 2012

“…These findings are supported by an earlier study, which demonstrated that JAK2 V617F monitoring post-transplant can predict relapse in patients who become mutation-positive after transplant (Steckel et al, 2007). Information on other molecular markers in the AHSCT setting for MF is limited, although, use of MPL (Thrombopoietin Receptor) mutation status as a MRD marker has been reported (Alchalby et al, 2010b;Rumi et al, 2010).…”

Reduced-Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis

“…The disappearance after transplantation of the MPLW515A mutation in one patient [42] and of the MPLW515L mutation in two patients [43] was reported by two different groups. Based on the experience with JAK2V617F, it might be expected that MPLW515L/K would become positive in the case of malignant relapse.…”

The CSF3R T618I mutation as a disease-specific marker of atypical CML post allo-SCT

“…[7][8][9][10] Such approaches would improve the detection sensitivity above that of Sanger sequencing and potentially allow quantitation of mutation level. Both persistence and eradication of the CSF3R T618I described above, correlating with the clinical course in both patients, indicate that serial monitoring of CSF3R mutations in aCML patients undergoing allo-SCT is a useful adjunct in the assessment of transplant efficacy.…”