A krónikus mieloproliferatív betegségek célzott terápiájának molekuláris alapjai

Translated title of the contribution: Molecular background of targeted therapy in chronic myeloproliferative diseases

Bödör Csaba, A. Matolcsy

Research output: Contribution to journalArticle

Abstract

The understanding of the molecular pathogenesis of malignant diseases allows for target specific and highly effective treatment of tumors. There are several successful ongoing studies in the field of chronic myeloproliferative disorders as well. Chronic myeloid leukemia (CML) is characterized by the constitutive activity of the BCR-ABL fusion tyrosine kinase resulting from the t(9; 22) translocation. The therapy of CML has been revolutionized by the introduction of imatinib, which targets the BCR-ABL protein and inhibits its kinase activity. A significant proportion of CML patients are resistant to imatinib, mainly because of the emergence of resistance mutations in abl gene. However, the second generation inhibitors (dasatinib, nilotinib) are active against all mutations, with exception of the T315I mutation. The discovery of the JAK2 V617F mutation in polycytaemia vera (PV), essential thombocytaemia (ET), and idiopathic myelofibrosis (PMF) has changed the classification and diagnosis of these entities. The Janus-2 kinase (JAK2) plays a key role in cell signaling, while the mutant form of the protein causes constitutive activation of different pathways, leading to malignant transformation of these cells. Since the discovery of the JAK2 V617F mutation raised the possibility of a success story similar to CML, development of JAK2 specific inhibitors in under intense investigation.

Original languageHungarian
Pages (from-to)193-202
Number of pages10
JournalOrvoskepzes
Volume84
Issue number3
Publication statusPublished - 2009

Fingerprint

Molecular Targeted Therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Disease
Mutation
abl Genes
Janus Kinase 2
Myeloproliferative Disorders
Primary Myelofibrosis
Mutant Proteins
Protein-Tyrosine Kinases
Phosphotransferases
Therapeutics
Neoplasms
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A krónikus mieloproliferatív betegségek célzott terápiájának molekuláris alapjai. / Csaba, Bödör; Matolcsy, A.

In: Orvoskepzes, Vol. 84, No. 3, 2009, p. 193-202.

Research output: Contribution to journalArticle

@article{99386e5137ee4346993d693d8478fa2b,
title = "A kr{\'o}nikus mieloproliferat{\'i}v betegs{\'e}gek c{\'e}lzott ter{\'a}pi{\'a}j{\'a}nak molekul{\'a}ris alapjai",
abstract = "The understanding of the molecular pathogenesis of malignant diseases allows for target specific and highly effective treatment of tumors. There are several successful ongoing studies in the field of chronic myeloproliferative disorders as well. Chronic myeloid leukemia (CML) is characterized by the constitutive activity of the BCR-ABL fusion tyrosine kinase resulting from the t(9; 22) translocation. The therapy of CML has been revolutionized by the introduction of imatinib, which targets the BCR-ABL protein and inhibits its kinase activity. A significant proportion of CML patients are resistant to imatinib, mainly because of the emergence of resistance mutations in abl gene. However, the second generation inhibitors (dasatinib, nilotinib) are active against all mutations, with exception of the T315I mutation. The discovery of the JAK2 V617F mutation in polycytaemia vera (PV), essential thombocytaemia (ET), and idiopathic myelofibrosis (PMF) has changed the classification and diagnosis of these entities. The Janus-2 kinase (JAK2) plays a key role in cell signaling, while the mutant form of the protein causes constitutive activation of different pathways, leading to malignant transformation of these cells. Since the discovery of the JAK2 V617F mutation raised the possibility of a success story similar to CML, development of JAK2 specific inhibitors in under intense investigation.",
keywords = "BCR-ABL, Dasatinib, Imatinib, JAK2 V617F, Tyrosine kinase inhibitor",
author = "B{\"o}d{\"o}r Csaba and A. Matolcsy",
year = "2009",
language = "Hungarian",
volume = "84",
pages = "193--202",
journal = "Orvoskepzes",
issn = "0030-6037",
publisher = "Semmelweis Kiado",
number = "3",

}

TY - JOUR

T1 - A krónikus mieloproliferatív betegségek célzott terápiájának molekuláris alapjai

AU - Csaba, Bödör

AU - Matolcsy, A.

PY - 2009

Y1 - 2009

N2 - The understanding of the molecular pathogenesis of malignant diseases allows for target specific and highly effective treatment of tumors. There are several successful ongoing studies in the field of chronic myeloproliferative disorders as well. Chronic myeloid leukemia (CML) is characterized by the constitutive activity of the BCR-ABL fusion tyrosine kinase resulting from the t(9; 22) translocation. The therapy of CML has been revolutionized by the introduction of imatinib, which targets the BCR-ABL protein and inhibits its kinase activity. A significant proportion of CML patients are resistant to imatinib, mainly because of the emergence of resistance mutations in abl gene. However, the second generation inhibitors (dasatinib, nilotinib) are active against all mutations, with exception of the T315I mutation. The discovery of the JAK2 V617F mutation in polycytaemia vera (PV), essential thombocytaemia (ET), and idiopathic myelofibrosis (PMF) has changed the classification and diagnosis of these entities. The Janus-2 kinase (JAK2) plays a key role in cell signaling, while the mutant form of the protein causes constitutive activation of different pathways, leading to malignant transformation of these cells. Since the discovery of the JAK2 V617F mutation raised the possibility of a success story similar to CML, development of JAK2 specific inhibitors in under intense investigation.

AB - The understanding of the molecular pathogenesis of malignant diseases allows for target specific and highly effective treatment of tumors. There are several successful ongoing studies in the field of chronic myeloproliferative disorders as well. Chronic myeloid leukemia (CML) is characterized by the constitutive activity of the BCR-ABL fusion tyrosine kinase resulting from the t(9; 22) translocation. The therapy of CML has been revolutionized by the introduction of imatinib, which targets the BCR-ABL protein and inhibits its kinase activity. A significant proportion of CML patients are resistant to imatinib, mainly because of the emergence of resistance mutations in abl gene. However, the second generation inhibitors (dasatinib, nilotinib) are active against all mutations, with exception of the T315I mutation. The discovery of the JAK2 V617F mutation in polycytaemia vera (PV), essential thombocytaemia (ET), and idiopathic myelofibrosis (PMF) has changed the classification and diagnosis of these entities. The Janus-2 kinase (JAK2) plays a key role in cell signaling, while the mutant form of the protein causes constitutive activation of different pathways, leading to malignant transformation of these cells. Since the discovery of the JAK2 V617F mutation raised the possibility of a success story similar to CML, development of JAK2 specific inhibitors in under intense investigation.

KW - BCR-ABL

KW - Dasatinib

KW - Imatinib

KW - JAK2 V617F

KW - Tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=82455216854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82455216854&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:82455216854

VL - 84

SP - 193

EP - 202

JO - Orvoskepzes

JF - Orvoskepzes

SN - 0030-6037

IS - 3

ER -