Contributions
Abstract: PB1621
Type: Publication Only
Background
Philadelphia chromosome (Ph), the result of a reciprocal translocation involving chromosomes 9 and 22: t(9;22)(q34;q11), is the most frequent genetic aberration in adult acute lymphoblastic leukemia (ALL) and is found in 15-30% patients. Additional chromosomal abnormalities are often found (~50%) in association with t(9;22)(q34;q11). The most common are: additional copy of Ph-chromosome (extra Ph), deletions del(22q) and del(7q), monosomy 7, trisomy 8 and others. Conventional chemotherapy programs that have been effective in other ALL cases have been unable to induce response in adults with Ph-positive ALL. Use of imatinib mesylate and other tyrosine kinase inhibitors as part of treatment have greatly improved the rates of complete hematologic and molecular remission in these patients. Imatinib interim therapy might improve the curative potential of allogeneic stem cell transplantation.
Aims
Aim of this study was to detect additional chromosomal abnormalities in adult patients with Philadelphia chromosome positive ALL and determine frequency of them.
Methods
Cytogenetic investigations of bone marrow and/or peripheral blood cells from 50 newly diagnosed adult patients with ALL were performed. The methods of conventional cytogenetics (GTG) and fluorescence in situ hybridization (FISH) were used.
Results
Cytogenetic investigations were performed in 50 newly diagnosed patients with ALL. Chromosomal aberrations of various kinds were found in 32 (64%) cases. According to the karyotype analysis patients were classified by risk groups: the group of patients with unfavorable cytogenetic markers (hypodiploidy, t(4;11)(q21;q23), t(9;22)(q34;q11), multiple changes (≥3)), the intermediate risk group without significant prognostic markers and the group with favorable prognostic factors (t(12;21)(p13;q22), high hyperdiploidy). Ph-chromosome was found in 8 (16%) cases. Five patients (62,5%), except for abnormal ones, had one or more normal metaphases in their karyotype. Of 8 patients with Ph-positive ALL, 3 (37,5%) had only Ph-chromosome, whereas other 5 (62,5%) – had additional cytogenetic abnormalities. Spectrum of additional chromosomal aberrations was as follows: extra Ph-chromosome and trisomy 8 (2 cases), extra Ph-chromosome and del(7)(q31) (1 case), trisomy 21 (1 case), high hyperdiploidy (57 chromosomes, extra Ph, trisomies X, 2, 4, 6, 8, 11, 14, 17, tetrasomy 21) (1 case). Cytogenetic investigations at relapse were performed in one case. Secondary chromosomal abnormalities in association with t(9;22)(q34;q11), both structural and numerical, were detected in this case, namely 1-2 additional copies of Ph, deletion del(1)(q24), trisomies 3, 6, 8 and marker chromosome. Presence of the additional/secondary chromosomal aberrations is the sign of clonal evolution and progression of disease and appears to have a significant deleterious effect on outcomes post allogeneic stem cell transplantation.
Conclusion
In our study frequency of Philadelphia chromosome in patients with ALL was 16%, which is comparable to the data reported in the literature. The most common additional chromosomal abnormalities in association with t(9;22)(q34;q11) were: extra Ph (80%) and trisomy 8 (60%). Presence of the additional/secondary chromosomal aberrations in Ph-positive cells is the sign of clonal evolution and disease progression.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia, Chromosomal abnormality, Philadelphia chromosome
Abstract: PB1621
Type: Publication Only
Background
Philadelphia chromosome (Ph), the result of a reciprocal translocation involving chromosomes 9 and 22: t(9;22)(q34;q11), is the most frequent genetic aberration in adult acute lymphoblastic leukemia (ALL) and is found in 15-30% patients. Additional chromosomal abnormalities are often found (~50%) in association with t(9;22)(q34;q11). The most common are: additional copy of Ph-chromosome (extra Ph), deletions del(22q) and del(7q), monosomy 7, trisomy 8 and others. Conventional chemotherapy programs that have been effective in other ALL cases have been unable to induce response in adults with Ph-positive ALL. Use of imatinib mesylate and other tyrosine kinase inhibitors as part of treatment have greatly improved the rates of complete hematologic and molecular remission in these patients. Imatinib interim therapy might improve the curative potential of allogeneic stem cell transplantation.
Aims
Aim of this study was to detect additional chromosomal abnormalities in adult patients with Philadelphia chromosome positive ALL and determine frequency of them.
Methods
Cytogenetic investigations of bone marrow and/or peripheral blood cells from 50 newly diagnosed adult patients with ALL were performed. The methods of conventional cytogenetics (GTG) and fluorescence in situ hybridization (FISH) were used.
Results
Cytogenetic investigations were performed in 50 newly diagnosed patients with ALL. Chromosomal aberrations of various kinds were found in 32 (64%) cases. According to the karyotype analysis patients were classified by risk groups: the group of patients with unfavorable cytogenetic markers (hypodiploidy, t(4;11)(q21;q23), t(9;22)(q34;q11), multiple changes (≥3)), the intermediate risk group without significant prognostic markers and the group with favorable prognostic factors (t(12;21)(p13;q22), high hyperdiploidy). Ph-chromosome was found in 8 (16%) cases. Five patients (62,5%), except for abnormal ones, had one or more normal metaphases in their karyotype. Of 8 patients with Ph-positive ALL, 3 (37,5%) had only Ph-chromosome, whereas other 5 (62,5%) – had additional cytogenetic abnormalities. Spectrum of additional chromosomal aberrations was as follows: extra Ph-chromosome and trisomy 8 (2 cases), extra Ph-chromosome and del(7)(q31) (1 case), trisomy 21 (1 case), high hyperdiploidy (57 chromosomes, extra Ph, trisomies X, 2, 4, 6, 8, 11, 14, 17, tetrasomy 21) (1 case). Cytogenetic investigations at relapse were performed in one case. Secondary chromosomal abnormalities in association with t(9;22)(q34;q11), both structural and numerical, were detected in this case, namely 1-2 additional copies of Ph, deletion del(1)(q24), trisomies 3, 6, 8 and marker chromosome. Presence of the additional/secondary chromosomal aberrations is the sign of clonal evolution and progression of disease and appears to have a significant deleterious effect on outcomes post allogeneic stem cell transplantation.
Conclusion
In our study frequency of Philadelphia chromosome in patients with ALL was 16%, which is comparable to the data reported in the literature. The most common additional chromosomal abnormalities in association with t(9;22)(q34;q11) were: extra Ph (80%) and trisomy 8 (60%). Presence of the additional/secondary chromosomal aberrations in Ph-positive cells is the sign of clonal evolution and disease progression.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Acute lymphoblastic leukemia, Chromosomal abnormality, Philadelphia chromosome