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R4 簡聖軒 指導老師: 高志平大夫.  Maturation of B lymphocyte  DLBCL classification  Double hit DLBCL  MYC/BCL-2 co-expression DLBCL  Conclusion and take home.

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Presentation on theme: "R4 簡聖軒 指導老師: 高志平大夫.  Maturation of B lymphocyte  DLBCL classification  Double hit DLBCL  MYC/BCL-2 co-expression DLBCL  Conclusion and take home."— Presentation transcript:

1 R4 簡聖軒 指導老師: 高志平大夫

2  Maturation of B lymphocyte  DLBCL classification  Double hit DLBCL  MYC/BCL-2 co-expression DLBCL  Conclusion and take home message

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4  Common morphologic variants  Centroblastic/immunoblastic/anaplastic  Rare morphologic variants  Molecular subgroups  Germinal centre B cell like(GCB)  Activated B cell like (ABC)  Immnuohistochemical subgroup  CD-5 (+) DLBCL  Germinal centre B cell like (GCB)  Non-germinal centre B cell like (non-GCB)

5 Nature 2000, 403:

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7  GCB: BCL6, CD 10  ABC: MYC, MUM1, CD44, FLIP, cyclin D2 Nature 2000, 403:

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10 16 case From CD20, CD10, Bcl-6, Mum-1, Bcl-2 CD138, MIB1, CD19, CD5, CD38 DLBCL with a germinal center (GC) profile. Progression free survival : 4 months Over all survival : 5 months Haematologica :92; 10, , 2007

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14  Chromosome breaks targeting the MYC gene located at the 8q24 in combination with additional rearrangement, such as BCL2,BCL6  MYC/BCL2 double hit lymphoma  extremely poor prognosis  Most GCB type Haematologica :92; 10, , 2007

15 307 cases (167 in training /140 in validation center) Detected MYC, BCL-2 by IHC MYC correlated with high MYC mRNA and MYC translocation Co expression of MYC and BCL-2 protein had inferior outcome

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19  Reviewed 893 cases  Tissue microarray immunohistochemical stain  FISH for MYC, BCL-2 and sequencing TP53  Gene expression profiling  COO classification: combined with GEP+IHC

20  64% MYC(+), 50% BCL-2(+)  34% MYC(+) + BCL-2(+)  19% MYC(-) + BCL-2(-) MYC+BCL2OthersP 5-yr OS30%75%< yr PFS27%73%<0.0001

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22 GCB ABC

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28 208 genes express differentially P<0.001 GCB: CD10 BCL-6 MYBL1 PI3KCG ABC: MUM1 cyclin D2 FLIP CD44 SLAP

29 No significant difference as P < gene express differentially as P < /20 gene also express in MYC/BCL-2(+) COO differentially

30 Total 153 genes were differentially expressed (P<0.001) 65 genes up-regulated 88 genes down-regulated

31  5-yrs OS/PFS <30 % in MYC/BCL co- expression  Correlated with poor prognosis factor: older age, advanced stage, extra-nodal, high IPI  29% DLBCL, expand the spectrum of aggressive DLBCL via IHC VS 3% double hit via genetic level

32  MYC/BCL-2 co-expression is more frequently observed in ABC subtype  MYC/BCL-2 co-expression contributes to the overall poor prognosis of this patient subset 1. Excluded MYC/BCL-2 (+), ABC ≒ GCB 2. In MYC/BCL-2 (+), ABC ≒ GCB 3. Difference in gene signatures between 2 subtypes was minimal in MYC/BCL-2 (-)

33  Down regulation of ECM, lack of cell-cell and cell-matrix adhesion may play a role in the high frequency of advanced stage and extra-nodal involvement  Inferior prognosis of patients with the ABC- DLBCL has been attributed to constitutive NF-kB activities

34  DLBCL is heterogeneous group  MYC/BCL-2 co-expression identified by IHC: poor prognosis, expand the spectrum of MYC/BCL-2 double hit in gene rearrangement  Assessment for MYC and BCL-2 protein expression more reliably predicts prognosis than COO classification

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