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MYC/BCL2 protein coexpression contributes inferior outcome in DLBCL

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Presentation on theme: "MYC/BCL2 protein coexpression contributes inferior outcome in DLBCL"— Presentation transcript:

1 MYC/BCL2 protein coexpression contributes inferior outcome in DLBCL
指導老師: 高志平大夫

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


4 DLBCL, NOS Common morphologic variants Rare 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 Distinct type of DLBCL by gene expression profiling
Nature 2000, 403:


7 Germinal center/ activated B cell
GCB: BCL6, CD 10 ABC: MYC, MUM1, CD44, FLIP, cyclin D2 Nature 2000, 403:



10 Double hit lymphoma 16 case From 1998-2006
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

11 Double hit lymphoma


13 Double hit lymphoma

14 Double hit in DLBCL 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 Co-expression MYC/BCL-2
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

16 MYC/BCL-2 VS others VS DHIT

17 Characters in cell origin


19 Method 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 Result 64% MYC(+), 50% BCL-2(+) 34% MYC(+) + BCL-2(+)
Others P 5-yr OS 30% 75% <0.0001 5-yr PFS 27% 73%

21 All VS subgroup comparsion

22 COO type result GCB ABC

23 IPI + DP result


25 MYC/BCL-2 vs COO

26 MYC/BCL-2 vs COO


28 GEP for MYC/BCL-2(+) ABC VS GCB
208 genes express differentially P<0.001 GCB: CD10 BCL-6 MYBL1 PI3KCG ABC: MUM1 cyclin D2 FLIP CD44 SLAP

29 GEP for MYC/BCL-2(-) ABC VS GCB
No significant difference as P <0.001 20 gene express differentially as P <0.01 13/20 gene also express in MYC/BCL-2(+) COO differentially

30 MYC/BCL2(+) VS MYC/BCL2(+)
Total 153 genes were differentially expressed (P<0.001) 65 genes up-regulated 88 genes down-regulated

31 Discussion 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 Discussion 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 Excluded MYC/BCL-2 (+), ABC ≒GCB In MYC/BCL-2 (+), ABC ≒GCB Difference in gene signatures between 2 subtypes was minimal in MYC/BCL-2 (-)

33 Discussion 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 Take home message 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

35 Thanks

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