Contributions
Abstract: PB1696
Type: Publication Only
Background
The Philadelphia (Ph) t(9;22)(q34;q11) results in an oncogenic BCR/ABL gene fusion, representing the hallmark of chronic myeloid leukemia (CML), although it has been also described in acute lymphoblatic (ALL) and myeloid (AML) leukemia. Three main different transcripts have been described (p210, p190 and p230), but rare atypical BCR breakpoints outside the cluster regions have been also reported and their clinical significance is under investigation. Atypical transcript p190 e6a2 is a rare fusion protein associated with aggressive phenotype and dismal prognosis. The breakpoint in BCR intron 6 is responsible for increased kinase activity and greater transforming potential because of the partial loss of the Guanine Exchange Factor (GEF)/dbl-like domain, completely absent in p190 proteins. This truncation could increase the BCR/ABL oncogenic activity.
Aims
In this report we describe 2 rare cases of Ph+ AML patients with the atypical p190 e6a2 isoform.
Methods
Routine morphologic, immunophenotypic and genetic analyses were carried out in all samples at diagnosis. cDNA extracted from bone marrow was synthesized from 1 μg of total RNA. Most common AML genetic alterations were investigated and a quantitative RT-PCR (qRT-PCR) for p190 transcripts was performed. qRT-PCR assay for FLT3-ITD and p190 e6a2 transcript were developed.
Results
Conclusion
The atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR/ABL transcripts may allow help to establish optimal treatment approaches on these aggressive BCR/ABL phenotypes.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Tyrosine kinase inhibitor, Philadelphia chromosome, BCR-ABL, Acute Myeloid Leukemia
Abstract: PB1696
Type: Publication Only
Background
The Philadelphia (Ph) t(9;22)(q34;q11) results in an oncogenic BCR/ABL gene fusion, representing the hallmark of chronic myeloid leukemia (CML), although it has been also described in acute lymphoblatic (ALL) and myeloid (AML) leukemia. Three main different transcripts have been described (p210, p190 and p230), but rare atypical BCR breakpoints outside the cluster regions have been also reported and their clinical significance is under investigation. Atypical transcript p190 e6a2 is a rare fusion protein associated with aggressive phenotype and dismal prognosis. The breakpoint in BCR intron 6 is responsible for increased kinase activity and greater transforming potential because of the partial loss of the Guanine Exchange Factor (GEF)/dbl-like domain, completely absent in p190 proteins. This truncation could increase the BCR/ABL oncogenic activity.
Aims
In this report we describe 2 rare cases of Ph+ AML patients with the atypical p190 e6a2 isoform.
Methods
Routine morphologic, immunophenotypic and genetic analyses were carried out in all samples at diagnosis. cDNA extracted from bone marrow was synthesized from 1 μg of total RNA. Most common AML genetic alterations were investigated and a quantitative RT-PCR (qRT-PCR) for p190 transcripts was performed. qRT-PCR assay for FLT3-ITD and p190 e6a2 transcript were developed.
Results
Conclusion
The atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR/ABL transcripts may allow help to establish optimal treatment approaches on these aggressive BCR/ABL phenotypes.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Tyrosine kinase inhibitor, Philadelphia chromosome, BCR-ABL, Acute Myeloid Leukemia