chronic phase leucemia mieloide cronica (cml) advanced phase
TRANSCRIPT
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Chronic phase
LEUCEMIA MIELOIDE CRONICA (CML)
Advanced phase
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•Effetti trascrizionali
FUNZIONI DI c-Abl
• Riconoscimento di lesioni a carico del DNA • Progressione del ciclo cellulare
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PRINCIPALI TERAPIE PER LA CML
• idrossiurea• interferone- (IFN- )• IFN- + araC• trapianto eterologo di cellule staminali• trapianto autologo di cellule staminali
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PI3 kinase
STAT5 NFB
Akt kinase
Bcl-xL
Bad
Bax
Bak
P
P
Caspase-3, -7
Cyt cSMAC
IAPs
Caspase-9
APAF-1, dATPCaspase-9
APOPTOSIS
BadP
Bcr-Abl
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Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.
A) Gruppo 3’-piridilico: aumenta l’attività cellulare del composto
B) Gruppo amidico: conferisce l’azione anti-TK
C) Gruppo metilico: abolisce l’azione anti-PKC
D) Gruppo N-metilpiperazinico: aumenta la solubilità e la biodisponibilità per via orale
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ALTRI BERSAGLI MOLECOLARI DEL GLIVEC
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Figure 16.25b The Biology of Cancer (© Garland Science 2007)
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Figure 16.30 The Biology of Cancer (© Garland Science 2007)
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Figure 16.26c The Biology of Cancer (© Garland Science 2007)
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Figure 16.27a (part 1 of 2) The Biology of Cancer (© Garland Science 2007)
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Figure 16.27a (part 2 of 2) The Biology of Cancer (© Garland Science 2007)
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Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.
Deininger, M. et al. Blood 2005;105:2640-2653
Figure 6. Frequency of BCR-ABL mutations detected in clinical specimens (n = 177)
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Gln Lys,Val
Thr Ile
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Figure 16.26b The Biology of Cancer (© Garland Science 2007)
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ULTERIORI APPLICAZIONI TERAPEUTICHE DEL GLIVEC
GISTGastrointestinal stromal tumors
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Figure 16.29 The Biology of Cancer (© Garland Science 2007)
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EFFETTI DEL GLIVEC SUL MICROAMBIENTE TUMORALE
• Inibizione degli effetti angiogenici del PDGF
sulle cellule dello stroma
sulle cellule endoteliali
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EFFETTI TOSSICI DEL GLIVEC
•Nausea; vomito•Ritenzione di liquidi•Crampi muscolari e dolori articolari•Mielosoppressione di grado 2-3•Cardiotossicità
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