Oncogenes in the myelodysplastic syndrome

Area of Science:

• Hematology
• Cancer Genetics
• Molecular Biology

Background:

• Normal haemopoietic stem cells undergo genetic alterations during the progression to myelodysplastic syndromes and leukaemia.
• Specific chromosomal abnormalities, frequently involving chromosomes 5 and 7, are observed in these conditions.

Purpose of the Study:

• To investigate the genetic changes associated with the transformation of normal haemopoietic stem cells into leukaemic cells.
• To identify key genes and chromosomal locations involved in preleukaemic processes.

Main Methods:

• Analysis of cytogenetic evidence to identify chromosomal abnormalities.
• Examination of gene mutations and translocations in leukaemic cells.

Main Results:

• Common chromosomal abnormalities involve chromosomes 5 and 7, which harbor genes regulating haemopoietic proliferation and differentiation (e.g., GM-CSF, IL-3, M-CSF).
• Oncogenes like met (chromosome 7q) and fms (chromosome 5q) may be deleted or translocated.
• Point mutations in the ras gene family are activated in myelodysplasia and acute myeloblastic leukaemia.

Conclusions:

• The progression to leukaemia involves progressive genetic changes in clonal populations.
• The precise cause, functional significance, and sequence of these genetic lesions remain unknown.