Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf ·...
Transcript of Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf ·...
![Page 1: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/1.jpg)
Linfoma di BurkittLinfoma di Burkitt
((BurkittBurkitt))
![Page 2: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/2.jpg)
AimsAims
…….Attitudes are more .Attitudes are more important than abilitiesimportant than abilities
Motives are more Motives are more important than methodsimportant than methods
Character is moreCharacter is moreimportant than clevernessimportant than cleverness
And heart takes precedence And heart takes precedence over the headover the head……....
Denis P. Burkitt, 1991Denis P. Burkitt, 1991
![Page 3: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/3.jpg)
LINFOMA DI BURKITT (LBT)LINFOMA DI BURKITT (LBT)
endemico: endemico: zone centrali dellzone centrali dell’’Africa (malaria)Africa (malaria)etetàà pediatrica; sedi: mandibola, pediatrica; sedi: mandibola, ovaioovaio
sporadico:sporadico: paesi occidentalipaesi occidentalietetàà variabile; sedi: intestino, variabile; sedi: intestino, gonadi, SNCgonadi, SNC
HIVHIV--correlatocorrelato:: SNC, etc.SNC, etc.
Buona risposta in etBuona risposta in etàà pediatrica con terapie aggressivepediatrica con terapie aggressive
![Page 4: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/4.jpg)
FORMA ENDEMICAFORMA ENDEMICA(Lancet Oncology 2004; 5:738(Lancet Oncology 2004; 5:738--46)46)
Patogenesi del linfoma di Burkitt endemico Patogenesi del linfoma di Burkitt endemico legata alla cooperazione di:legata alla cooperazione di:-- EBVEBV (immortalizzazione),(immortalizzazione),-- malariamalaria (spinta proliferativa),(spinta proliferativa),-- ArbovirusArbovirus trasmessi da mosche (stimolo trasmessi da mosche (stimolo immunitario),immunitario),-- Euphorbia tirucalliEuphorbia tirucalli (danno al DNA),(danno al DNA),-- traslocazione coinvolgente traslocazione coinvolgente cc--MYCMYC..
![Page 5: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/5.jpg)
LINFOMA DI BURKITTLINFOMA DI BURKITT
MORFOLOGIA:MORFOLOGIA: endemico/sporadico= isomorfiendemico/sporadico= isomorfitaglia media omogeneataglia media omogeneacromatina reticolarecromatina reticolare22--6 nucleoli6 nucleolicitoplasma basofilo/citoplasma basofilo/vacuolatovacuolatocrescita coesivacrescita coesivamitosi numerosissimemitosi numerosissimeaspetto a cielo stellatoaspetto a cielo stellato
![Page 6: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/6.jpg)
LBT: dettagli citologiciLBT: dettagli citologiciin un caso con in un caso con colonizcoloniz--
zazionezazione ““follicolarefollicolare””
![Page 7: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/7.jpg)
LINFOMA DI BURKITTLINFOMA DI BURKITT
FENOTIPO:FENOTIPO: SIgMSIgM++
marcatori Bmarcatori B++
CD10CD10++
BclBcl--66++
BclBcl--22--
cc--mycmyc++
MibMib--11++ = 100%= 100%
![Page 8: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/8.jpg)
CD10CD10 BclBcl--66
![Page 9: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/9.jpg)
BclBcl--22
![Page 10: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/10.jpg)
KiKi--6767MIB1MIB1
![Page 11: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/11.jpg)
GENOTIPOGENOTIPO
LBT endemico: LBT endemico: EBVEBV++
t(8;14)t(8;14)
LBT sporadico :LBT sporadico : EBV+: 25% HIVEBV+: 25% HIV--
50% HIV50% HIV++
t (2;8)t (2;8)t(8;22)t(8;22)diversi diversi breakpointsbreakpointsp53 (?)p53 (?)p21 (?)p21 (?)
Sul cromosoma 8: gene cSul cromosoma 8: gene c--MYCMYC
![Page 12: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/12.jpg)
Cristina Campidelli, Lynnette Cristina Campidelli, Lynnette TumwineTumwine, Pier Paolo Piccaluga, , Pier Paolo Piccaluga, Stefano A PileriStefano A Pileri
BURKITT LYMPHOMA IN UGANDA IN THE THIRD MILLENNIUM: BURKITT LYMPHOMA IN UGANDA IN THE THIRD MILLENNIUM: A MORPHOLOGIC AND MOLECULAR APPRAISAL ON TISSUE A MORPHOLOGIC AND MOLECULAR APPRAISAL ON TISSUE
MICROMICRO--ARRAYARRAY
![Page 13: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/13.jpg)
HIV infection and c-MYC status in endemic Burkitt lymphomaCampidelli, C., Gazzola, A., Vitone, F., Tumwine, L., and Pileri, S.A.Hum. Pathol., 39:1408-9, 2008.
Hum. Pathol., 39:817-823, 2008.
![Page 14: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/14.jpg)
Patient and material collectionPatient and material collection•• 95 cases from Ugandan tribes95 cases from Ugandan tribes
•• 22--64 64 ysys (median age: 16)(median age: 16)
•• Site of involvement:Site of involvement:-- lymph node lymph node (34 cases)(34 cases)-- abdomen abdomen (26 cases)(26 cases)-- gonads gonads (25 cases)(25 cases)-- jaw jaw (10 cases)(10 cases)
•• formalin fixed paraffin embedded blocks punched formalin fixed paraffin embedded blocks punched and collected in 2 TMA blocks (48 and 47 cases and collected in 2 TMA blocks (48 and 47 cases each)each)
![Page 15: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/15.jpg)
TMA technologyTMA technology
![Page 16: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/16.jpg)
![Page 17: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/17.jpg)
![Page 18: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/18.jpg)
Results Results •• Positivity forPositivity for BB--cell markerscell markers, CD10 and Bcl, CD10 and Bcl--66
•• Negativity for BclNegativity for Bcl--22
•• KiKi--67 67 close toclose to 100%100%
•• ThirtyThirty--five CD30+ cases (37%)five CD30+ cases (37%)
•• Expression of CD38 in 73 cases (77%) and CD138 in 43 Expression of CD38 in 73 cases (77%) and CD138 in 43 cases (45%)cases (45%)
•• IRFIRF--4 mostly negative (7 positive cases)4 mostly negative (7 positive cases)
•• Constant EBV integrationConstant EBV integration
![Page 19: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/19.jpg)
CD30CD30
![Page 20: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/20.jpg)
CD138CD138
![Page 21: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/21.jpg)
EBEREBER
![Page 22: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/22.jpg)
HIVHIV--statusstatus
•• None of the samples showed HIV integrationNone of the samples showed HIV integration
•• HIVHIV--1 DNA was investigated by:1 DNA was investigated by:RTRT--PCR amplifying gag region (142 bp)PCR amplifying gag region (142 bp)nested PCR amplifying env region (248 bp)nested PCR amplifying env region (248 bp)
Driver GA et al. J Driver GA et al. J VirolVirol Methods, 2007Methods, 2007BrachtelBrachtel EF et al. AIDS Res Hum Retroviruses, 2002 EF et al. AIDS Res Hum Retroviruses, 2002 StrappeStrappe PM et al. J PM et al. J VirolVirol Methods, 1998Methods, 1998
![Page 23: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/23.jpg)
FISH analysisFISH analysis•• FISH failed to demonstrate t(8;14) FISH failed to demonstrate t(8;14) due due to DNA degradationto DNA degradation
•• Surrogated by immunohistochemistrySurrogated by immunohistochemistry
•• Characteristic expression patterns of TCL1, CD38, and Characteristic expression patterns of TCL1, CD38, and CD44 identify aggressive lymphomas harboring a MYC CD44 identify aggressive lymphomas harboring a MYC translocation translocation ((RodigRodig SJ, Am J SJ, Am J SurgSurg PatholPathol, 2008) , 2008)
•• 64 out of 85 cases were TCL1+, CD38+ and CD4464 out of 85 cases were TCL1+, CD38+ and CD44--•• 9 out of 85 cases were TCL19 out of 85 cases were TCL1--, CD38+ and CD44, CD38+ and CD44--•• 9 out of 85 cases were TCL1+, CD389 out of 85 cases were TCL1+, CD38-- and CD44and CD44--•• 3 out of 85 cases were TCL13 out of 85 cases were TCL1--, CD38, CD38-- and CD44and CD44--
![Page 24: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/24.jpg)
TCL1TCL1
![Page 25: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/25.jpg)
CD38CD38
![Page 26: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/26.jpg)
CD44CD44
![Page 27: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/27.jpg)
![Page 28: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/28.jpg)
![Page 29: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/29.jpg)
QuestionQuestion
•• Are the three subtypes of Burkitt Are the three subtypes of Burkitt
lymphoma different diseases or different lymphoma different diseases or different
features of the same disease?features of the same disease?
![Page 30: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/30.jpg)
Piccaluga PP, De Piccaluga PP, De FalcoFalco G, G, KustagiKustagi K, K, GazzolaGazzola A, A, AstolfiAstolfi A, Agostinelli C, A, Agostinelli C, LeucciLeucci E, E, OnnisOnnis A, A, TripodioTripodio C, C, SapienzaSapienza MR, MR, BellanBellan C, C, LazziLazzi S, S, TumwineTumwine L, L, MawandaMawanda M, M, OgwangOgwang M, M, CalbiCalbi V, Formica S, Califano A, Pileri V, Formica S, Califano A, Pileri SA and SA and LeonciniLeoncini L: Gene expression L: Gene expression analysis uncovers similarity and analysis uncovers similarity and differences among Burkitt lymphoma differences among Burkitt lymphoma subtypes. Blood 2011, Esubtypes. Blood 2011, E--pub ahead of pub ahead of print. print.
Burkitt lymphomaFollicular lymphomaDiffuse large B-cell lymphomaPrimary mediastinal B-cell lymphomaChronic lymphocytic leukemiaNormal B-cells
Molecular profiling of Molecular profiling of BL subtypesBL subtypes
BL is a unique molecular BL is a unique molecular entityentity
![Page 31: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/31.jpg)
BL subtypes are all related to GC cells & presents BL subtypes are all related to GC cells & presents several deregulated genes and cellular programsseveral deregulated genes and cellular programs
SPARCSPARC BLBLGerminal Center B cellsGerminal Center B cells
+1+1 --11
NaNaïïveve
GerminalGerminal center Bcenter B --cellscells
MemoryMemory
BLBL
GreyGrey zonezone
GCGC N/MN/M
+1+1 --11
NaiveNaiveGerminalGerminal center B center B cellscellsMemoryMemoryBLBL
GreyGrey zonezone
GCGC N/MN/M
1,000 genes1,000 genes
•• immune response immune response •• proliferation (MYC)proliferation (MYC)•• adhesion adhesion •• NOTCH signalingNOTCH signaling
![Page 32: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/32.jpg)
Though similar, BL subtypes present Though similar, BL subtypes present differences in their differences in their GEPsGEPs
eBL sBL HIV-BLeBLeBL sBLsBL HIVHIV-BLBL eBLHIV-BLsBL
eBLeBLHIVHIV --BLBLsBLsBL
![Page 33: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/33.jpg)
eBLeBLsBLsBL
eBLeBLHIVHIV--BLBL
eBL and HIVeBL and HIV--BL: 16 genes BL: 16 genes (almost identical),(almost identical),
eBL & sBL: 254 genes, including eBL & sBL: 254 genes, including cell cycle regulation.cell cycle regulation.
Though similar, BL subtypes present Though similar, BL subtypes present differences in their differences in their GEPsGEPs
![Page 34: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/34.jpg)
eBL (TAT & HIVeBL (TAT & HIV--BL)BL)
![Page 35: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/35.jpg)
GSEA showed that eBL and sBL differ for the GSEA showed that eBL and sBL differ for the expression of genes related to the RBL2 network expression of genes related to the RBL2 network
RBL2 functional network identified byRBL2 functional network identified byARACNeARACNe
eBLeBLsBLsBL
The results do not vary byThe results do not vary bysubtracting the MYC networksubtracting the MYC network
Accordingly, RBL2 malfunction isAccordingly, RBL2 malfunction is relevant for eBL relevant for eBL but doesnbut doesn’’t affect sBL.t affect sBL.
![Page 36: Linfoma di Burkitt (L-B) - Benvenuto su AMS Campus ...campus.unibo.it/81112/19/03_Burkitt.pdf · HIV-correlato:SNC, etc. Buona risposta in età pediatrica con terapie aggressive.](https://reader031.fdocuments.in/reader031/viewer/2022013008/5ca0260988c99312188ca3a2/html5/thumbnails/36.jpg)
ConclusionsConclusions1.1. Irrespective of the subtypes, BL is a unique molecular Irrespective of the subtypes, BL is a unique molecular
entity distinct from other Bentity distinct from other B--NHLs.NHLs.2.2. All BL subtypes are related to GC BAll BL subtypes are related to GC B--cells.cells.3.3. Genes and cellular programs deregulated in BL have Genes and cellular programs deregulated in BL have
been identified, including cell cycle and proliferation been identified, including cell cycle and proliferation control, NOTCH signaling and immune response.control, NOTCH signaling and immune response.
4.4. GEP differences do exist among BL subtypes.GEP differences do exist among BL subtypes.5.5. In particular, RBL2 malfunction seems to characterize In particular, RBL2 malfunction seems to characterize
the signature of eBL (and HIVthe signature of eBL (and HIV--BL?) suggesting a BL?) suggesting a possible involvement of such gene in BL pathogenesis.possible involvement of such gene in BL pathogenesis.