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Significance of MLL gene aberrations in patients with acute myeloid leukemia
Šárová, Iveta ; Březinová, Jana (advisor) ; Král, Jiří (referee)
4 ABSTRACT Significance of MLL gene aberrations in patients with acute myeloid leukemia In acute myeloid leukemia (AML), predominantly in AML M5a, the most frequent recurrent aberration of chromosome 11 involves region 11q23. Molecular breakpoint studies of several translocations involving chromosomal band 11q23 led to the detection of a gene that was named MLL (myeloid/lymphoid leukemia). Since that time, more than 70 different translocation partners of the MLL gene have been described. This gene is important for the proper HOX gene expression during ontogenesis and hematopoiesis. Chromosomal aberrations affecting the MLL gene occur in 5 - 10 % of AML cases and are very variable. Aberrations of the MLL gene are associated with an aggresive type of the disease and its detection is needed for the treatment decision. Therefore, we investigated the occurrence of MLL abnormalities in bone marrow cells of the 66 newly diagnosed AML patients, using conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses with a commercially available MLL Break Apart Rearrangement probe (Abbott VYSIS). Out of the 66 patients, we proved MLL abnormalities in 9 (13,6%): 5 (7,6%) showed translocation of MLL gene, in 3 (4,5%) we detected MLL gene amplification without any evidence of rearrangement and in 1 (1,5%)...
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Significance of MLL gene aberrations in patients with acute myeloid leukemia
Šárová, Iveta
In acute myeloid leukemia (AML), predominantly in AML M5a, the most frequent recurrent aberration of chromosome 11 involves region 11q23. Molecular breakpoint studies of several translocations involving chromosomal band 11q23 led to the detection of a gene that was named MLL (myeloid/lymphoid leukemia). This gene is important for the proper HOX gene expression during ontogenesis and hematopoiesis. Chromosomal aberrations affecting the MLL gene occur in 5 - 10 % of AML cases and are very variable. Since that time, more than 70 different translocation partners of the MLL gene have been described. Aberrations of the MLL gene are associated with an aggresive type of the disease and its detection is needed for the treatment decision. Therefore, we investigated the occurrence of MLL abnormalities in bone marrow cells of the 66 newly diagnosed AML patients, using conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses with a commercially available MLL Break Apart Rearrangement probe (Abbott VYSIS). Out of the 66 patients, we proved MLL abnormalities in 9 (13,6%): 5 (7,6%) showed translocation of MLL gene, in 3 (4,5%) we detected MLL gene amplification without any evidence of rearrangement and in 1 (1,5%) pacient only an extra copy of the MLL gene. The FISH results were verified by...
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Chromosomal aberrations in childhood acute leukemia.
Sládková, Lucie ; Zemanová, Zuzana (advisor) ; Šárová, Iveta (referee)
1 Abstract Leukemias are the most common cancer diseases in childhood. The majority of cases represent acute leukemias, the most common of which is acute lymphoblastic leukemia (ALL), the second most frequent subtype is acute myeloid leukemia (AML). One of the basic laboratory examinations at the time of diagnosis is the cytogenetic analysis of the karyotype of leukemic cells in which we are looking for the recurrent chromosomal aberrations. These changes in the structure or number of the chromosomes can be found in up to 90 % of patients and the exact prognostic significance is known for most of them. In ALL, the findings of high hyperdiploidy (>50 chromosomes) and translocation t(12;21)(p13;q22) are considered the most significant prognostic factor associated with good prognosis and translocations involving the KMT2A gene in the 11q23 region are associated with poor prognosis. In AML, the most frequent aberrations are t(8;21)(q22;q22), t(15;17)(q24;q21) and inv(16)(p13;q22) which are considered indicator of good prognosis. An important unfavourable prognostic finding in AML are the KMT2A gene rearrangements, the most common of which is the translocation t(9;11)(q23;p13.1). Nowadays, there are many ways to detect chromosomal aberrations in leukemic cells. G-banding is the most common method of classical...
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Molecular-cytogenetic analysis of chromosome 11 aberrations in hematological malignancies
Šárová, Iveta ; Březinová, Jana (advisor) ; Goetz, Petr (referee) ; Jarošová, Marie (referee)
Chromosome 11 abnormalities are found in many hematological malignancies. In acute myeloid leukemia (AML), a proto-oncogene MLL (11q23.3) is frequently altered. However, rearrangements to other regions of chromosome 11 have been reported. Therefore, we have identified and characterized the chromosome 11 breakpoints and common deleted and amplified areas in the bone marrow or peripheral blood cells of newly diagnosed patients with AML. Many recurrent and random chromosome 11 breakpoints were identified (recurrent in bands 11p15.4 (in NUP98 gene), 11q23.3 (in the MLL gene), 11p13, 11p12 and 11q13.2) and deleted or duplicated/amplified regions were determined. We notified new possibly significant genes in the development of AML. Contrary to the MLL rearrangements, patients with other chromosome 11 changes were older, with complex karyotype, unbalanced aberrations and short survival. FISH screening was proved very helpful in case of deviding cells lack and cryptic MLL gene rearrangement. In conclusion, molecular analyses of chromosomal breakpoints and amplified or deleted areas are very important not only for the patient stratification into specific prognostic and clinical subgroups but also for the identification of genes involved in tumour pathogenesis. Further investigation of the affected genes and...
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Significance of MLL gene aberrations in patients with acute myeloid leukemia
Šárová, Iveta
In acute myeloid leukemia (AML), predominantly in AML M5a, the most frequent recurrent aberration of chromosome 11 involves region 11q23. Molecular breakpoint studies of several translocations involving chromosomal band 11q23 led to the detection of a gene that was named MLL (myeloid/lymphoid leukemia). This gene is important for the proper HOX gene expression during ontogenesis and hematopoiesis. Chromosomal aberrations affecting the MLL gene occur in 5 - 10 % of AML cases and are very variable. Since that time, more than 70 different translocation partners of the MLL gene have been described. Aberrations of the MLL gene are associated with an aggresive type of the disease and its detection is needed for the treatment decision. Therefore, we investigated the occurrence of MLL abnormalities in bone marrow cells of the 66 newly diagnosed AML patients, using conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses with a commercially available MLL Break Apart Rearrangement probe (Abbott VYSIS). Out of the 66 patients, we proved MLL abnormalities in 9 (13,6%): 5 (7,6%) showed translocation of MLL gene, in 3 (4,5%) we detected MLL gene amplification without any evidence of rearrangement and in 1 (1,5%) pacient only an extra copy of the MLL gene. The FISH results were verified by...
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Significance of MLL gene aberrations in patients with acute myeloid leukemia
Šárová, Iveta ; Březinová, Jana (advisor) ; Král, Jiří (referee)
4 ABSTRACT Significance of MLL gene aberrations in patients with acute myeloid leukemia In acute myeloid leukemia (AML), predominantly in AML M5a, the most frequent recurrent aberration of chromosome 11 involves region 11q23. Molecular breakpoint studies of several translocations involving chromosomal band 11q23 led to the detection of a gene that was named MLL (myeloid/lymphoid leukemia). Since that time, more than 70 different translocation partners of the MLL gene have been described. This gene is important for the proper HOX gene expression during ontogenesis and hematopoiesis. Chromosomal aberrations affecting the MLL gene occur in 5 - 10 % of AML cases and are very variable. Aberrations of the MLL gene are associated with an aggresive type of the disease and its detection is needed for the treatment decision. Therefore, we investigated the occurrence of MLL abnormalities in bone marrow cells of the 66 newly diagnosed AML patients, using conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses with a commercially available MLL Break Apart Rearrangement probe (Abbott VYSIS). Out of the 66 patients, we proved MLL abnormalities in 9 (13,6%): 5 (7,6%) showed translocation of MLL gene, in 3 (4,5%) we detected MLL gene amplification without any evidence of rearrangement and in 1 (1,5%)...
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