4a. B Leucemie Acute Linfoidi - LAL
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Transcript of 4a. B Leucemie Acute Linfoidi - LAL
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HEMATOPOIESIS
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- A CELLULE B (LAL B)
- A CELLULE T (LAL T)
LEUCEMIA ACUTA LINFOBLASTICA
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Maturazione funzionale del linfocita B
BONE MARROW
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TRASLOCAZIONI COINVOLGENTI LA BANDA 14q32
Autori Casi 14q32/ casi anormali
Traslocazioni bilanciate (singoli casi)
Cabanillas (1988)
5/18 t(11;14)(q23;q32) t(14;18)(q32;q21)
Hossfeld (1978)
2/6 t(10;14)(q22:q32)
Reeves (1980) 4/8
Schwartze (1982)
2 t(1;14)(p2?3?1;q32)
Tilly (1991) 3/31 t(2;14)(p11;q32)
Poppema (1988)
6/23 t(14;18)(q32;q21) t(10;14)(q23;q32)
Schlegelberger (1994)
1/14 t(14;19)(q32;p13)
Fulcuhara and Rowley (ref. Schouten 1991)
1 t(1;14)(q2;q32)
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Bone marrow aspirate
t(8;14)(q24;q32)
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t(8;14)(q24;q32)
- Leucemia acuta linfoblastica L3 e Linfoma di Burkitt
- Endemica (EBV)
- Sporadica
- Localizzazione extramidollare
- Malattia aggressiva
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Gene C-MYC: proteina nucleare
Funzioni: . progressione del ciclo cellulare e proliferazione (attivo fasi G0-M da vari fatt di crescita. Regola sintesi di DNAin fase S)
. differenziazione (modifiche livelli di espressione in varie fasi di differenziazione,…..) . Apoptosi
HLH (helix-loop-helix domain): Dominio di legame al DNA, fattore di trascrizione
Leucine zipper domain: Dominio di dimerizzazione
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Linfoma di Burkitt endemico
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HEMATOPOIESIS
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14q11
TCR
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TRASLOCAZIONI COINVOLGENTI LA BANDA 14Q11
Autori Traslocazioni Bilanciate Döhner (1992) t(14;18)(q11;p11)
Tilly (1991) t(13;14)(p11;q11) t(14;15)(q11;p11)
Schlegelberger (1994) t(14;17)(q11;q11) t(14;19)(q11;p13.2)
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MLL Genomic Locus
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MLL/11q23Transcriptional regulatory factor
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11q23/MLL
- Gene promiscuo
- Numerosi partners
-Riarrangiato in LAL (B e T), LAM, LA bifenotipiche, LAM
-Leucemie acute primarie e secondarie
(trattamento con inibitori della topoisomerasi II)
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Krivtsov AV. Nat Rev Cancer. 2007 Nov;7(11):823-33
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t(4;11)(q21;q23)
der(4) der(11)
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t(4;11)(q21;q23)
AF4/4q21 MLL/11q23
fusion protein: 5’ MLL-3’AF10 (240Kb)
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CD19+, CD10-, B-ALL (pro-B)biphenotypic ALAML M4/M5Organomegaly (CNS involvement)unfavorable prognosis
Congenital (<1 year old)Secondary ( epipodophyllotoxins, topoisomerase II ihibitors)
Entità clinico-ematologiche
t(4;11)(q21;q23)
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t(12;21)(p13;q22)
- Traslocazione cromosomica reciproca criptica
- Non visibile alla citogenetica convenzionale
- Necessaria FISH o analisi molecolare
- Ricombinazione ETV6-AML1
- Perdita allele normale di ETV6
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t(12;21)(p13;q22)
Cryptic
Translocation
Cryptic
Translocation & Deletion
AML1-ETV6
ETV6-AML1
AML1-ETV6
ETV6-AML1
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Geni targetETV6/AML1
CoRepCoRepRepressore Trascrizionale
ESPRESSIONE:ETV6/AML1
Geni target
AML1
CBFBAttivatore Trascrizionale
Core binding factor
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LAL / PROGNOSITraslocazioni Geni Tipo di LAL Prognosi
t(9;22)(q34;q11) BCR-ABL B-ALL, mixed ALL Sfavorevole
t(11;…)(q23;…) MLL B-ALL, T-ALL Sfavorevole
t(4;11)(q21;q23) MLL-AF4 B-ALL, mixed ALL Sfavorevole
t(12,21)(p13;q22) ETV6-AML1 PRE-B ALL Favorevole
t(8;14)(q24;q32) IgH-MYC L3 Sfavorevole
t(14; )(q11; ) TCRAD T-ALL Sfavorevole
t(1;19)(q23;p13.3) Iperdiploidia>50 Ipodiploidia
PBX-E2A B-ALL Sfavorevole Favorevole Sfavorevole