Molecular biology of bcr-abl1-positive chronic myeloid leukemia

Alfonso Quintás-Cardama, Jorge Cortes

Research output: Contribution to journalReview article

Abstract

Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL 1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the onco-genic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.

Original languageEnglish (US)
Pages (from-to)1619-1630
Number of pages12
JournalBlood
Volume113
Issue number8
DOIs
StatePublished - Feb 19 2009

Fingerprint

Molecular biology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Molecular Biology
Phosphotransferases
Stem cells
Tumors
Repair
Blast Crisis
Genomic Instability
DNA
Phase Transition
Oncogenes
Research
DNA Repair
Neoplasms
Stem Cells
Imatinib Mesylate

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Molecular biology of bcr-abl1-positive chronic myeloid leukemia. / Quintás-Cardama, Alfonso; Cortes, Jorge.

In: Blood, Vol. 113, No. 8, 19.02.2009, p. 1619-1630.

Research output: Contribution to journalReview article

Quintás-Cardama, Alfonso ; Cortes, Jorge. / Molecular biology of bcr-abl1-positive chronic myeloid leukemia. In: Blood. 2009 ; Vol. 113, No. 8. pp. 1619-1630.
@article{916092ec02094d779087d5d9a53e4c67,
title = "Molecular biology of bcr-abl1-positive chronic myeloid leukemia",
abstract = "Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL 1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the onco-genic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.",
author = "Alfonso Quint{\'a}s-Cardama and Jorge Cortes",
year = "2009",
month = "2",
day = "19",
doi = "10.1182/blood-2008-03-144790",
language = "English (US)",
volume = "113",
pages = "1619--1630",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

TY - JOUR

T1 - Molecular biology of bcr-abl1-positive chronic myeloid leukemia

AU - Quintás-Cardama, Alfonso

AU - Cortes, Jorge

PY - 2009/2/19

Y1 - 2009/2/19

N2 - Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL 1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the onco-genic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.

AB - Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL 1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the onco-genic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.

UR - http://www.scopus.com/inward/record.url?scp=61849163272&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61849163272&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-03-144790

DO - 10.1182/blood-2008-03-144790

M3 - Review article

C2 - 18827185

AN - SCOPUS:61849163272

VL - 113

SP - 1619

EP - 1630

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -