Biclonal expansion and heterogeneous lineage involvement in a case of chronic myeloproliferative disease with concurrent MPL~(W5515L)/JAK2~(V617F) mutation

摘要

Chronic myeloproliferative diseases (CMPDs)/myeloproliferative neoplasms (MPNs) are caused by clonal mutations of tyrosine kinase or receptor genes such as BCR-ABL, JAK2~(V617F), and MPL~(W5515L) Recently, we and others showed that these mutations may be combined in hematopoietic cells of some MPN cases. It is not yet clear whether, in cases with a double mutation, subclonal evolution has taken place or whether 2 unrelated clones proliferate independently. To address this issue, bone marrow and peripheral blood cells in a case of unclassifiable MPN (Figure S1, available on the Blood website; see the Supplemental Materials link at the top of the online article) with combined JAK2~(V617F) and MPL~(W5515L) mutation were separated by laser microdissection as well as fluorescence-activated cell sorting, followed by quantitative analysis of mutated allele burden by pyrosequencing