AML with t(7;21)(p22;q22): A new recurrent semi- cryptic RUNX1 rearrangement M. Sales 1 , N. Foster 1 , S. Tauro 2 , J. Cunningham 1 , N. Pratt 1 Departments of Cytogenetics 1 and Haematology 2 Ninewells Hospital, Dundee ACC Spring Meeting Liverpool 2008
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AML with t(7;21)(p22;q22): A new recurrent semi-cryptic RUNX1 rearrangement M. Sales 1, N. Foster 1, S. Tauro 2, J. Cunningham 1, N. Pratt 1 Departments.
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AML with t(7;21)(p22;q22):A new recurrent semi-cryptic
RUNX1 rearrangement
M. Sales1, N. Foster1, S. Tauro2, J. Cunningham1, N. Pratt1
WCP7 & TEL/AML1 extra signal probe tetraploid cell
der(7)
der(7)
der(21)
der(21)
Ideograms
7 21 7 21
Hiller B, Bradtke J, Balz H and Rieder H (2004): "CyDAS Online Analysis Site", http://www.cydas.org/OnlineAnalysis/"
t(7;21)
Paulsson et al (2006): Patient info
• 7 yr old boy - Presented March 1995 Pyrexic tonsillitis & cervical adenitis Hypercellular BM Blasts difficult to classify morphologically Immunophenotyping = AML M0
• Treatment – initially by NOPHO-AML-93 protocol After induction still 25% blasts 3 additional chemotherapy blocks - CR Allogeneic stem cell transplant (sister) June 1995 Relapse March 2000 – abnormal cytogenetics 2nd CR April 2000 followed by donor lymphocyte infusions
• Patient still OK April 2005
Paulsson et al (2006): Genetics
• Apparently normal male at diagnosis
• Karyotype at relapse46,XY,t(4;6)(q24;p11),del(5)(q15),t(11;18)(q23;q21)[24]
• t(7;21)(p22;q22) found while screening paediatric leukaemia's for t(7;21)(q36;p13)
• Initially detected by WCP for chromosome 7
• LSI TEL/AML1 extra signal probe (Vysis)
• RUNX1 rearranged with USP42 (complex)
Paulsson et al (2006): Findings
• USP42 – protease in ubiquitin pathway
• Highly expressed in skeletal muscle, liver & pancreas and weakly in brain, placenta & heart.
• Also in normal BM and 1o AMLs
• Fusion protein is thought to have a dominant-negative effect on normal RUNX1 and may retain USP42 protease activity
Conclusion
• Lack of a visible cytogenetic abnormality does not preclude chimeric genes
• cryptic rearrangements previously reported in AML MLL/ARHGEF12 - del(11q) MLL/CBL - del(11q) Nup98/NSD1 - t(5;11)(q35;p15.5)
• Now add t(7;21) to list
• Others likely – MFISH/SKY & aCGH
• Larger study required to assess actual frequency and clinical implications (UKCCG coordinated)
AML with t(7;21)(p22;q22):A new recurrent semi-cryptic
RUNX1 rearrangement
M. Sales1, N. Foster1, S. Tauro2, J. Cunningham1, N. Pratt1