Overcoming Chronic Myeloid Leukemia Stem Cell Resistance to Imatinib by Also Targeting JAK2
Menée in vitro et in vivo, cette étude met en évidence un mécanisme d'interaction entre les protéines AHI-1, BCR-ABL et JAK2 justifiant l'intérêt d'un traitement combinant un inhibiteur de JAK2 avec l'imatinib pour surmonter une résistance à l'imatinib chez les patients atteints d'une leucémie myéloïde chronique
Chronic myeloid leukemia (CML) originates in the hematopoietic stem cell because of a reciprocal translocation of chromosomes 9 and 22. This translocation juxtaposes the ABL1 proto-oncogene with BCR, which translates into a constitutively active BCR-ABL kinase that drives expansion of leukemic progeny. Treatment of CML with ABL kinase inhibitors such as imatinib is very effective and brings about complete cytogenetic response in more than 80% of newly diagnosed patients.
CML is a celebrated model disease because of its stem cell origin, straightforward oncogene, targeted therapy, easy monitoring, and high odds of remission.
I remember treating patients with CML in the pre-imatinib era. Interferon-
α was the standard of care, and the patients were miserable because of feverish side effects and frequent injections. When we opened our first clinical trial of imatinib in the late 1990s, one particular Veterans Health Administration (VA) patient whose CML responded wonderfully on study was distraught because he faced the possibility of being cured of his disease and that meant a possible loss of his VA health benefits. To mixed fortune, we continued imatinib in this patient out of fear of relapse.
Since that time, we
’ve learned that despite low to undetectable levels of …
Journal of the National Cancer Institute , commentaire, 2013