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09 April 2009

Molecular and phenotypic variability in consecutive blast crises in CML patient

Krzysztof Lewandowski, Marta Baranska, Michal Gniot, Lidia Gil, Anna Czyz, Małgorzata Iwoła, Mieczyslaw Komarnicki

Am J Case Rep 2009; 10:39-43 :: ID: 869622

Abstract

Background: The mechanisms of chronic myeloid leukemia (CML) transformation into a blast crisis (BC) are not fully understood.
Case Report: We report a case of an acute myeloid leukemia with normal karyotype successfully treated with autologous stem cell transplantation (SCT). Two years later the patient developed CML (p210BCR-ABL positive) that was treated with imatinib. BCs of changing immunophenotype (biphenotypic, biclonal, myeolomonoblastic, monoblastic, myeloblastic) were diagnosed in the next four years. CML was treated with allogeneic SCT from an unrelated donor. In the post-transplant period a disappearance of p210BCR-ABL and conversion to p190BCR-ABL was documented. Moreover, a molecular study of p210 transcript revealed the presence of F311L mutation. Sequencing of p190BCR-ABL has shown a presence of both mutant (F311L) and native BCR-ABL. Three months after the transplantation hematological remission was lost and symptoms of BC resistant to dasatinib were documented.
Conclusions: We hypothesize that p190 has been derived from the existing p210 Philadelphia chromosome. It would be possible if a deletion of 36–92 kb fragment from the Philadelphia chromosome (BCR exons 2-14 and a part of intron 1) occurred, however the alternative splicing seems to be more probable explanation. It cannot be also excluded that p210BCR-ABL and p190BCR-ABL originated from different subclones of leukemic cells. This may confirm the oligoclonality of CML in presented case.

Keywords: blast crises, chronic myeloid leukemia, phenotypic and genotypic variability, Stem Cell Transplantation, tyrosine kinase inhibitors

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923