Subclones with the t(9;22)/BCR-ABL1 rearrangement occur in AML and seem to cooperate with distinct genetic alterations.
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Subclones with the t(9;22)/BCR-ABL1 rearrangement occur in AML and seem to cooperate with distinct genetic alterations. / Bacher, Ulrike; Haferlach, Torsten; Alpermann, Tamara; Zenger, Melanie; Hochhaus, Andreas; Beelen, Dietrich W; Uppenkamp, Michael; Rummel, Mathias; Kern, Wolfgang; Schnittger, Susanne; Haferlach, Claudia.
In: BRIT J HAEMATOL, Vol. 152, No. 6, 6, 2011, p. 713-720.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Subclones with the t(9;22)/BCR-ABL1 rearrangement occur in AML and seem to cooperate with distinct genetic alterations.
AU - Bacher, Ulrike
AU - Haferlach, Torsten
AU - Alpermann, Tamara
AU - Zenger, Melanie
AU - Hochhaus, Andreas
AU - Beelen, Dietrich W
AU - Uppenkamp, Michael
AU - Rummel, Mathias
AU - Kern, Wolfgang
AU - Schnittger, Susanne
AU - Haferlach, Claudia
PY - 2011
Y1 - 2011
N2 - 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 (0·5%), 2:272 AML cases with t(8;21)/RUNX1-RUNX1T1 (0·7%), 1:1029 NPM1-mutated AML (0·1%), 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.
AB - 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 (0·5%), 2:272 AML cases with t(8;21)/RUNX1-RUNX1T1 (0·7%), 1:1029 NPM1-mutated AML (0·1%), 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.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Retrospective Studies
KW - Gene Rearrangement
KW - Karyotyping
KW - Translocation, Genetic
KW - Leukemia, Myeloid, Acute/genetics
KW - Chromosome Banding/methods
KW - Chromosomes, Human, Pair 22/genetics
KW - Chromosomes, Human, Pair 9/genetics
KW - Core Binding Factors/genetics
KW - Fusion Proteins, bcr-abl/genetics
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Retrospective Studies
KW - Gene Rearrangement
KW - Karyotyping
KW - Translocation, Genetic
KW - Leukemia, Myeloid, Acute/genetics
KW - Chromosome Banding/methods
KW - Chromosomes, Human, Pair 22/genetics
KW - Chromosomes, Human, Pair 9/genetics
KW - Core Binding Factors/genetics
KW - Fusion Proteins, bcr-abl/genetics
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
M3 - SCORING: Journal article
VL - 152
SP - 713
EP - 720
JO - BRIT J HAEMATOL
JF - BRIT J HAEMATOL
SN - 0007-1048
IS - 6
M1 - 6
ER -
