Molecular Cytogenetics Group
Group Leader: Dr Elisabeth Nacheva
The discovery by my team of the cryptic deletions affecting the balanced chromosome translocation t(9;22) in patients suffering from Philadelphia positive chronic myeloid leukaemia (CML) has laid the foundation of my current interest in the genome imbalances of Ph(+) disorders.
Our early adoption of genomic array technology (aCGH) allows us to screen CML samples for genome aberrations leading to a greater understanding of the mechanisms of disease progression (Fig 1).
While genome loss, frequently cryptic, is uniquely associated with the lymphoid blast transformation (e.g. IKZF1 and CDKN2A genes on chromosomes 7 and 9 respectively), gains of chromosome regions 8q21/24, 17q11/24 and 19p are frequently present in myeloid blast transformation of CML (Fig 2). Genetic variations such as these shed light on the processes underlying disease onset and development. Current investigations include a review of the genomic profile of early progenitor cells (CD34+) in chronic disease searching for tell tale signs associated with the development of more aggressive stages of CML. Another study explores the rare Ph(+) form of acute myeloid leukaemia (AML) for associations with other BCR/ABL1 positive diseases eg CML and Ph(+) acute lymphocytic leukaemia (ALL).
As a pioneer in the use of FISH for research and diagnostics, I have a longstanding interest in the development of new fluorescent probes for the detection of fusion genes, amplifications and deletions. This has led us to the identification of the chromosome telomere region as site for genomic integration of the HHV6 virus(Fig 3) and to our current programme for screening bone marrow donors treated with GCSF for possible genomic changes.
• A Chanalaris - Post doc
• M Valganob - Research assoc
• A Virgilli - PhD student
• D Brazma MD Research assoc
• J Howard-Reeves - Research assoc