Lymphomas & myelomas Flashcards
What stage of maturation of B cells are those below involved & what CD markers are expressed
FL, DLBCL, Myeloma
FL: Germinal centre B cell: CD19, CD20+
DLBCL: Germinal centre B cell: CD19, CD20+
Myeloma: Plasma cell: CD27+, CD138
What is somatic hypermutation?
extremely high rate of mutation >= 10^5-10^6
describe the TP53/17 cen deletion probe
a) type of probe
b) interpretation of result
a) locus specific indicator probe: G at centromere & R at 17p13
b) Normal: 2G, 2R
Deletion TP53: 2G, 1R
Monosomy: 1G, 1R
describe the CDKN2C (1p del)/ CKS1B (1q amp) probe
a) type of probe
b) interpretation of result
a) locus specific indicator probe: G at 1p & R at 1q
b) Normal: 2G, 2R
1 q Amp: 2G, 3R
Trisomy 1: 3G, 3R
Genetic mechanism associated with deletion at 1p (CDKN2C)
CDKN2C > cyclin-dependent kinase inihibitor. important in proliferation of B cells
Genetic mechanism associated with amplification at 1q (CKS1B )
CKS1B > binds to & activates cyclin-dependent kinase
overexpression => inc cell growth & poor prognosis in various cancers
describe the hyperdiploidy probe
a) type of probe
b) interpretation of result
a) locus specific indicator probe: G at 5, A at 9, & R at 15
b) Normal: 2G, 2A 2R
Hyperdiploidy: 3G, 3A 3R
Genetic mechanism associated with hyperdiploidy
extra copies => gene dosage effect => various genes de-regulated & oncogene proteins produced
What’s the std risk cytogen. markers for myeloma?
Hyperdiploidy of 5, 9, 15 w/ no High risk cytogen.markers (otherwise it overrides this classification)
What’s the High risk cytogen. markers for myeloma? (4)
- t(4;14)
- t(14;16)
- p53 deletion
- 1p deletion/amplification
What’s the cytogen. markers for follicular lymphomas?
t(14;18)(q:q) IGH::BCL2
What’s the cytogen. markers for DLBCL (diffused large B-cell leukaemia)? (5)
& prognosis
• Complex karyotype (>4 changes) • TP53 mutations • t(14;18) IGH::BCL2 • t(3;V) IGH::BCL6 • t(8;14) IGH::MYC Prognosis: shorter survival
Genetic mechanism of ooncogenesis of follicular lymphomas t(14;18)
t(14;18)(q:q) IGH::BCL2
IGH on 14 = promoter region => overexpression of BCL2 (stop cell death) => proliferation of neoplastic cells
Genetic mechanism of ooncogenesis of DLBCL t(3;V) e.g t(3;3) & t(3;18)
GH on 3 > regulatory region
t(3;3) IGH::BCL6
BCL2 on 3 > inhibits germinal B-cell diff. & inflammation
t(3;18) IGH::BCL2
BCL6 on 18 > protein inhibts cell death
=> Overpression of BCL2/6 = proliferation
Presentation FL, DLBCL, myeloma (what sites in the body)
FL: localised nodes ++, 50% BM
DLBCL: +- localised nodes, rarely in BM
Myeloma: BM involvement
