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Cytogenetic Findings in Chronic Lymphocytic Leukemia
- • Deletion 13q14 (50%) (good prognosis if sole abnormality)
- • Deletion 11q22 (ATM) (poor prognosis)
- • Deletion 17p13 (p53) (poor prognosis)
- • Trisomy 12 (20%) impact on prognosis unresolved)
- 2 molecular subtypes based on maturation of B cell:
- • Mutated: Somatic hypermutation of IGH variable region (lower risk)
- • Unmutated: >98% homology to germline (higher risk)
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Cytogenetic Findings in Multiple Myeloma
- 1) Hyperdiploid sub-group:
- • Significantly better overall survival
- • Gains involving primarily +3, +5, +7, +9, +11, +15,
- +19, +21
- • Infrequent structural abnormalities
- 2) Hypodiploid sub-group:
- • More aggressive clinical course
- • Strongly correlated with complex structural
- rearrangements
- • 14q32 translocations
- • Monosomy 13 or partial deletion of chr 13 (13q14)
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Cytogenetic Findings in Myelodysplastic Syndromes
- Good risk:
- • Normal karyotype
- • Isolated del(5q)
- • Isolated del(20q)
- • -Y
- Poor risk:
- • Complex abnormalities (i.e. ≥ 3 abnormalities)
- • -7 or del(7q)
- Intermediate Risk:
- • All other abnormalities
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Cytogenetic Findings in Chronic Myelogenous Leukemia
- • t(9;22)(q34;q11) BCR-ABL1
- • 90-95% of cases have t(9;22) at diagnosis
- Breakpoint in BCR determines size of BCR-ABL1 fusion protein
- • Major breakpoint region: p210 (210 kilodaltons)
- • μ breakpoint cluster: p230 (230 kilodaltons)
- Additional chromosomal aberrations associated with progression include:
- +8, isochromosome 17q, additional
- Ph chromosome +der(22)
- • Quantitative RT-PCR for BCL-ABL1 fusion transcript used to assess for response to imatinib
- • Imatinib competes with ATP for binding to BCR-ABL1 kinase domain
- • Point mutations that prevent drug binding to BCR-ABL1 kinase domain can lead to drug resistance
- • T315I mutation: resistant to imatinib & other kinase inhibitors
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