Contributions
Abstract: PB1690
Type: Publication Only
Background
In 10-12% of patients with acute myeloid leukemia (AML) in bone marrow cells, complex karyotype (CK) is present in their initial cytogenetic evaluation. It is traditionally regarded as a poor prognostic factor, particularly in patients showing dicentric chromosomes.
Aims
The aim of the study was to review karyotypes of AML patients with CK and to verify the presence of dicentric chromosomes (DCs) by FISH with multi-centromeric probes. The frequency and prognostic significance of DCs in AML was evaluated as well.
Methods
During years 2006–2016, 607 adult patients with newly diagnosed AML (excluding the specific subtype of AML-M3) were examined by conventional cytogenetics. The complex aberrations were investigated using multicolor fluorescence in situ hybridization (mFISH) and multicolor banding (mBAND). Monosomies were verified with the XCyting Centromere Multi-Color Probe Mix (MetaSystems), which is able to distinguish 18 chromosomal pairs in one test, and/or with a Vysis chromosome enumeration (CEP) probe (Abbott) and/or Satellite Enumeration (SE) FISH Probes SE 13/21 and SE 14/22 (Kreatech Diagnostics).
Results
CK was proved in 114 (19%) adult AML patients at diagnosis. Monosomy was detected in 63% of patients by conventional cytogenetics/mFISH, respectivly in 55% by centromeric FISH. Some of the losses were revised as the presence of a hidden DC. The use of centromeric FISH proved the increase of frequency of DCs in adult AML patients with CK from 27% (31/114) to 51% (58/114). In total, 79 dicentric, 2 tricentric, 1 quadricentric, and 12 isodicentric chromosomes were identified. DCs were often formed by chromosomes 17 and 20. Some DCs were observed repeatedly, however the breakpoints were not recurrent.
Conclusion
FISH analysis revealed high frequency of DCs in adult AML patients, particularly in bone marrow cells with complex karyotypes. Unbalanced aberrations leading to chromosomal losses indicate possible presence of hidden DC or its previous existence. DCs undergo variety of stabilization changes and can produce secondary monocentric derivative chromosome. DCs participate in raising of chromosomal instability (additional aberrations and new DCs) resulting in the clonal evolution of abnormal cells, which is associated with the adverse course of the disease and short survival of patients.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Chromosomal instability, Molecular cytogenetics
Abstract: PB1690
Type: Publication Only
Background
In 10-12% of patients with acute myeloid leukemia (AML) in bone marrow cells, complex karyotype (CK) is present in their initial cytogenetic evaluation. It is traditionally regarded as a poor prognostic factor, particularly in patients showing dicentric chromosomes.
Aims
The aim of the study was to review karyotypes of AML patients with CK and to verify the presence of dicentric chromosomes (DCs) by FISH with multi-centromeric probes. The frequency and prognostic significance of DCs in AML was evaluated as well.
Methods
During years 2006–2016, 607 adult patients with newly diagnosed AML (excluding the specific subtype of AML-M3) were examined by conventional cytogenetics. The complex aberrations were investigated using multicolor fluorescence in situ hybridization (mFISH) and multicolor banding (mBAND). Monosomies were verified with the XCyting Centromere Multi-Color Probe Mix (MetaSystems), which is able to distinguish 18 chromosomal pairs in one test, and/or with a Vysis chromosome enumeration (CEP) probe (Abbott) and/or Satellite Enumeration (SE) FISH Probes SE 13/21 and SE 14/22 (Kreatech Diagnostics).
Results
CK was proved in 114 (19%) adult AML patients at diagnosis. Monosomy was detected in 63% of patients by conventional cytogenetics/mFISH, respectivly in 55% by centromeric FISH. Some of the losses were revised as the presence of a hidden DC. The use of centromeric FISH proved the increase of frequency of DCs in adult AML patients with CK from 27% (31/114) to 51% (58/114). In total, 79 dicentric, 2 tricentric, 1 quadricentric, and 12 isodicentric chromosomes were identified. DCs were often formed by chromosomes 17 and 20. Some DCs were observed repeatedly, however the breakpoints were not recurrent.
Conclusion
FISH analysis revealed high frequency of DCs in adult AML patients, particularly in bone marrow cells with complex karyotypes. Unbalanced aberrations leading to chromosomal losses indicate possible presence of hidden DC or its previous existence. DCs undergo variety of stabilization changes and can produce secondary monocentric derivative chromosome. DCs participate in raising of chromosomal instability (additional aberrations and new DCs) resulting in the clonal evolution of abnormal cells, which is associated with the adverse course of the disease and short survival of patients.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Chromosomal instability, Molecular cytogenetics