Journal article

Publication year: 2011

Pages: 713-720

Journal: British Journal of Haematology

Volume number: 152

Issue number: 6

ISSN: 0007-1048

eISSN: 1365-2141

Open access status: Bronze

DOI Link: https://doi.org/10.1111/j.1365-2141.2010.08472.x

Publisher: Wiley

Abstract: 
P>In AML, cooperation of mutations suppressing differentiation ('class-II-mutations') with 'class-I-mutations' increasing cell proliferation is frequent. In rare cases of myeloid malignancies, the BCR-ABL1 fusion was reported to cooperate as class-I-mutation with class-II-mutations, but most cases had to be classified as blast phase of chronic myeloid leukaemia (CML). We identified five cases of Philadelphia positive subclones in AML occurring in coincidence with other genetic lesions: 1:220 patients with inv(16)/CBFB-MYH11 (0 center dot 5%), 2:272 AML cases with t(8;21)/RUNX1-RUNX1T1 (0 center dot 7%), 1:1029 NPM1-mutated AML (0 center dot 1%), and one patient with s-AML following MDS with a 5q-deletion. Four patients had m-BCR (e1a2) BCR-ABL1 transcripts; one case only had an M-BCR (b3a2) breakpoint. These cases allow some interesting conclusions: The BCR-ABL1 rearrangement apparently can cooperate with the NPM1 mutation similar to other class-I-mutations. The identification of Philadelphia positive subclones in < 1% of patients with CBF-leukaemias fits well with previous observations that most CBF-AML are accompanied by activating mutations in genes enhancing proliferation. Since we observed the occurrence of the Philadelphia positive subclones at diagnosis, at relapse, or throughout the disease, the time point of the emergence of Philadelphia subclones seems variable in AML. Clinical research should further concentrate on Philadelphia positive subclones in AML to assess the clinical impact.

Harvard Citation style: Bacher, U., Haferlach, T., Alpermann, T., Zenger, M., Hochhaus, A., Beelen, D., et al. (2011) Subclones with the t(9;22)/BCR-ABL1 rearrangement occur in AML and seem to cooperate with distinct genetic alterations, British Journal of Haematology, 152(6), pp. 713-720. https://doi.org/10.1111/j.1365-2141.2010.08472.x

APA Citation style: Bacher, U., Haferlach, T., Alpermann, T., Zenger, M., Hochhaus, A., Beelen, D., Uppenkamp, M., Rummel, M., Kern, W., Schnittger, S., & Haferlach, C. (2011). Subclones with the t(9;22)/BCR-ABL1 rearrangement occur in AML and seem to cooperate with distinct genetic alterations. British Journal of Haematology. 152(6), 713-720. https://doi.org/10.1111/j.1365-2141.2010.08472.x