Cibler les cellules souches leucémiques pour éliminer la LMC

[cousineg]

'L’objectif de cibler efficacement les cellules souches leucémiques fait miroiter la possibilité d’éliminer la source du problème et, un jour, d’éliminer la LMC.'
Extrait de la page WEB http://www.cmlsource.ca/origins.php?lang=2"

[sergio]

J'ai lu cet article avec beaucoup d'intérêt. Cette approche intelligente de tentative de neutralisation du transcrit bcr-abl peut s'appliquer à toutes les méloproliférations à condition d'être capable d'identifier les cellules souches malignes. Ces travaux sont d'un grand intérêt aussi pour les leucémies aiguês myéloblastiques qui relèvent de la même démarche. Par contre, il ne semble pas que ces travaux puissent apporter de nouvelles approches de la leucémie myélodysplasique. Les porteurs de mélofibrose reteront pour l'insta,t au bord de la route..........
Enfin, un progrès qui sera bon à prendre lorsqu'il débouchera sur de nouvelles thérapies, mais il est à craindre que ce ne soit pas pour demain.

[cousineg]

'In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib'
Blood First Edition Paper, prepublished online May 12, 2010; DOI 10.1182/blood-2009-11-255109
'It is not clear if absence of BCR-ABL transcripts - complete molecular response (CMR) - is synonymous with, or required for, cure of chronic myeloid leukemia (CML). Some patients achieve CMR with imatinib (IM), but most relapse shortly after treatment discontinuation. Furthermore, most patients in long-term remission (LTR) post stem cell transplantation (SCT) are considered 'functionally cured', although some remain occasionally positive for low level BCR-ABL mRNA. Interpretation of the latter is complicated since it has been observed in healthy individuals. We designed a patient-specific, highly sensitive, DNA quantitative PCR to test follow-up samples for the original leukemic clone, identified by its unique genomic BCR-ABL fusion (gBCR-ABL). In 5 IM-treated patients in CMR, gBCR-ABL was detected in transcript-negative samples; 4 patients became gBCR-ABL-negative with continuing IM therapy. In contrast, out of 9 patients in LTR (13-27 years) post-SCT, gBCR-ABL was detected in only 1, despite occasional transcript-positive samples in 8 of them. In conclusion, in IM-treated patients, absence of transcripts should not be interpreted as absence of the leukemic clone, although continuing IM after achievement of CMR may lead to further reduction of residual disease. Post-SCT, we found little evidence that the transcripts occasionally detected originate from the leukemic clone. '
Extrait de http://bloodjournal.hematologylibrary.o ... 1-255109v1

[cousineg]

Combination Therapy Targets Stubborn Leukemia Stem Cells
ScienceDaily (May 17, 2010)
'New research discovers a combination of drugs that may prove to be a more effective treatment for a lethal form of leukemia. The study, published by Cell Press in the May issue of the journal Cancer Cell, reports that the new therapeutic strategy effectively targets notoriously intractable leukemia stem cells that often escape standard treatment and are a main factor in disease relapse.
....
Dr. Bhatia and colleagues were interested in examining whether histone deacetylase inhibitors (HDACi) that have shown some promise as a treatment for several other cancers, might be effective at eliminating CML stem cells. HDACi were of interest because they not only target rapidly dividing cancer cells but also have been shown to eliminate non-proliferating cancer cells. The researchers found that treatment with a combination of HDACi and IM effectively reduced CML cells that were resistant to IM alone. Further, a combination of HDACi and IM markedly diminished leukemia stem cells in a mouse model of CML
.....
The researchers include Bin Zhang, City of Hope National Medical Center, Duarte, CA; Adam C. Strauss, City of Hope National Medical Center, Duarte, CA; Su Chu, City of Hope National Medical Center, Duarte, CA; Min Li, City of Hope National Medical Center, Duarte, CA; Yinwei Ho, City of Hope National Medical Center, Duarte, CA; Keh-Dong Shiang, City of Hope National Medical Center, Duarte, CA; David S. Snyder, City of Hope National Medical Center, Duarte, CA; Claudia S. Huettner, Dana-Farber Cancer Institute, Boston, MA; Leonard Shultz, The Jackson Laboratory, Bar Harbor, ME; Tessa Holyoake, University of Glasgow, Scotland, UK; and Ravi Bhatia, City of Hope National Medical Center, Duarte, CA.'
Extrait de http://www.sciencedaily.com/releases/20 ... 132842.htm

[cousineg]

Loss of the Alox5 gene impairs leukemia stem cells and
prevents chronic myeloid leukemia, July 2009
Yaoyu Chen, Yiguo Hu, Haojian Zhang, Cong Peng & Shaoguang Li
Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA. Present address: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. Correspondence should be addressed to S.L. (Shaoguang.Li@umassmed.edu).
'Targeting of cancer stem cells is believed to be essential for curative therapy of cancers, but supporting evidence is limited. Few
selective target genes in cancer stem cells have been identified. Here we identify the arachidonate 5-lipoxygenase (5-LO) gene
(Alox5) as a critical regulator for leukemia stem cells (LSCs) in BCR-ABL–induced chronic myeloid leukemia (CML). In the
absence of Alox5, BCR-ABL failed to induce CML in mice. This Alox5 deficiency caused impairment of the function of LSCs
but not normal hematopoietic stem cells (HSCs) through affecting differentiation, cell division and survival of long-term LSCs
(LT-LSCs), consequently causing a depletion of LSCs and a failure of CML development. Treatment of CML mice with a 5-LO
inhibitor also impaired the function of LSCs similarly by affecting LT-LSCs, and prolonged survival. These results demonstrate that
a specific target gene can be found in cancer stem cells and its inhibition can completely inhibit the function of these stem cells.''
Extrait de http://www.unav.es/ciencias/estudios/do ... s09def.pdf