RNA'SEQUENCING'ANALYSIS'IN'PRIMARY'MEDIASTINAL'B'CELL'LYMPHOMA:'
POSTER'3'
IDENTIFICATION'OF'DIFFERENT'GENE'EXPRESSION'RELATED'TO'
CHEMORESISTANCE'
'
Guido! Eugenio! Parvis1,! Danny! Incarnato2,! Davide! Torti3,! Ubaldo! Familiari4,! Francesco! Vassallo5,!
Giovanna! Carrà3,! Salvatore! Oliviero5,! Marco! Volante3,! Angelo! Guerrasio3,! Giuseppe!
Saglio3!and!Alessandro!Morotti3!
!
(1)AUO!Mauriziano,!Torino,!Italy,!(2)University!of!Groningen,!Groningen,!Netherlands,!(3)University!of!
Turin,!Orbassano,!Italy,!(4)Dept!of!Patology,!Aosta,!Italy,!(5)University!of!Turin,!Torino,!Italy!
!
Background:!Primary!mediastinal!large!B!cell!lymphoma!(PMLBCL)!is!a!rare!subtype!of!nonJ
Hodgkin! lymphoma! mostly! diagnosed! in! young! women! and! is! currently! recognized! as! a!
distinct!clinical!and!biological!entity.!First!line!therapy!with!RJCHOP!allows!to!achieve!good!
remission!rates!even!if!chemoresistant!cases!remain!highly!challenging!from!the!therapeutic!
standpoint.! As! such,! we! aimed! to! compare! the! transcriptome! of! RJCHOP! resistant! PMBCL!
patients!to!those!of!chemosensitive!patients.!
Methods:!We! extracted! RNA! from! embedded! paraffin! samples! and! then! we! performed!
whole!RNA!sequencing!on!7!patients.!Four!of!them!were!selected!as!chemoresistant!(Group!
A),! while! three! of! them! were! classified! as! responder! to! RJCHOP! (Group! B).! A! First!
bioinformatics!analysis!selected!a!panel!of!200!genes!significantly!differentially!expressed!in!
chemoresistant! (A)! samples! versus! chemosensitive! (B).! An! unbiased! analysis! based! on!
different! ontology! of! the! genes! led! to! easily! identify! common! signatures! that! may! better!
profile! the! two! groups! of! patients.! Finally,! on! a! bias! analysis,! genes! were! divided! into!
categories!in!order!to!identify!potential!new!targets!and/or!mechanisms!of!chemoresistance.!
Results:!We! identified! three! genes! which! may! be! frankly! related! to! chemoresistance! in!
PMLBCLs!due!to!an!overexpression!in!the!group!A!or!a!suppression!of!expression!in!group!B.!
We! selected! NFKBIA,! the! gene! which! encodes! for! the! IκBα! protein,! mutated! in! numerous!
Hodgkin's! lymphoma! cells,! which! cause! NFkB! to! be! chronically! active! in! the! lymphoma!
tumor!cells.!For!this!reason,!we!imagine!that!it!could!have!a!major!role!in!the!modulation!of!
PMLBCLs!sensitivity!to!chemotherapy.!
EPHB1!was!selected!for!its!very!strong!expression!in!the!poor!prognosis!group,!since!it!is!one!
of!the!most!expressed!genes!and!for!his!association!with!numerous!cancers.!The!kinase!STK!
33! appeared! overexpressed! in! group! A.! A! more! thorough! investigation! of! this! gene! might!
lead!to!new,!significant!findings.!
Conclusions:'!
Our! in! silico! analyses! allowed! to! identify! in! PMBCL! an! unique! profile! that! may! modulate!
sensitivity!to!chemotherapy.!Further!analyses!may!address!whether!this!unique!phenotype!
has! clinical! implications.! We! may! expect! to:! i)! develop! specific! therapeutic! strategies! to!
target! NFkB,! EPHB1! and! STK33! pathways! in! PMBCL! with! a! chemoresistant! behaviour;! ii)!
correlate!the!expression!profile!of!resistant!PMBCL!to!other!transcriptomes,!including!those!
of! Hodgkin! Lymphomas,! Diffuse! Large! B! cell! Lymphomas,! in! order! to! better! profile! those!
clinical!and!biological!overlapping!features.!
' '
SCIENTIFIC PROGRAMME
SESSION I
HODGKIN’S DISEASE
DEBATE I
IS THERE STILL A ROLE
FOR COMBINED MODALITY
THERAPY FOR EARLY
STAGE CHL?
SESSION II
T-CELL LYMPHOMA
ROUNDTABLE I
FUTURE DIRECTIONS IN
T-CELL LYMPHOMA
SESSION III
FOLLICULAR LYMPHOMA
DEBATE II
CAN WE AVOID
CHEMOTHERAPY IN
THE MANAGEMENT OF
FOLLICULAR LYMPHOMA?
SESSION IV
RARE LYMPHOMAS –
MARGINAL ZONE
LYMPHOMA AND
WALDENSTRÖM M
ACROGLOBULINEMIA
ROUNDTABLE II – WHERE
TO GO IN RARE B-CELL
LYMPHOMAS
SESSION V
MANTLE CELL LYMPHOMA
SESSION VI
DIFFUSE LARGE B-CELL
LYMPHOMA
DEBATE III
DO WE STILL NEED ASCT
IN MCL?
SESSION VII
NOVEL THER APEUTIC
CONCEPTS IN B-CELL
LYMPHOMAS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES