Combination of pioglitazone with tyrosine kinase inhibitor    - CML - Chronic myeloid leukemia

Important notice: You must inform your CML doctor or a qualified doctor before using this drug. The material presented here is for information purposes only;  it is not a substitute for your physician’s guidance and care. The side-effects of pioglitazone would also to be taken into account if this treatment were to be offered in routine care.  

" ​Philippe Leboulch, M.D., a professor of medicine and cell biology at the University of Paris, and colleagues temporarily administered pioglitazone in addition to imatinib to three patients with chronic myeloid leukemia.

​The researchers note that glitazones are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). They report that activation of PPARγ by the glitazones reduces expression of STAT5 and the downstream targets HIF2α5 and CITED26, guardians of the quiescence and stemness of CML leukemia stem cells.
"When pioglitazone was given temporarily to three chronic myeloid leukemia patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained complete molecular response, up to 4.7 years after withdrawal of pioglitazone," the authors write. "This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."
Extract of     Addition of Glitazone to Chemo May Help Treat CML by Pratice Update


"Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α5 and CITED26, which are key guardians of the quiescence and stemness of CML LSCs.

When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."

Extract of    Prost S, Relouzat F, Spentchian M, et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature. 2015. doi:10.1038/nature15248


More about pioglitazone ​with wikipedia
​
ARTICLES

Five-Year Follow-up of the Phase I/II Discontinuation Trial of Imatinib after Pioglitazone (EDI-PIO) in Chronic Myeloid Leukemia Patients in Deep Molecular Response
​December 12, 2022, ASH 2022  

Efficacy and safety of pioglitazone in a phase 1/2 imatinib discontinuation trial (EDI‐PIO) in chronic myeloid leukemia with deep molecular response
August 30, 2020,  American Journal of Hematology

Pioglitazone Did Not Affect PPAR-Γ, STAT5, HIF2α and CITED2 Gene Expression in Chronic Myeloid Leukemia Patients with Deep Molecular Response
December 7, 2019, ASH 2019    

Prescribing Trend of Pioglitazone After Safety Warning Release in Korea
November 19, 2019, AJMC
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Adding Oral Pioglitazone to Standard Induction Chemotherapy of Acute Myeloid Leukemia: A Randomized Clinical Trial
January 2019, Clinical Lymphoma, Myeloma & Leukemia

Abstract 1835: PPARγ agonist in combination with bcr/abl tyrosine kinase inhibitors in patients of chronic myeloid leukemia in chronic phase with suboptimal molecular response
July 2018, Cancer Research

In emerging area of ‘diabetic lung disease,’ pioglitazone may play preventive role
July 16, 2018, Healio

Pilot Study of Imatinib Discontinuation in Patients with Chronic Myeloid Leukemia with Deep Molecular Response (EDI-PIO) – Evaluation of Pioglitazone in Treatment-Free Remission
December 2017, ASH2017

Pioglitazone Prevents Stroke in Patients with a Recent TIA or Ischemic Stroke: A Planned Secondary Analysis of the IRIS Trial
October 30, 2017, Circulation
 
Pioglitazone And Metformin (Precautions)   WARNING
March 1, 2017, Mayo Clinic

Pioglitazone Plus Imatinib Leads to Molecular Response in Patients With Chronic-Phase Chronic Myeloid Leukemia
January 25, 2017, ASH clinicals news

Adding Pioglitazone Could Improve Molecular Response in CML Patients
Janvier 6, 2017, Cancer Network

Adding Pioglitazone to Imatinib May Improve Response Rate in CML
January  4, 2017,  Cancer Therapy Advisor

Pioglitazone could induce remission in major depression: a meta-analysis
December 2016, Altmetric

Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study                                             ********* must be seen ******
December 27, 2016, Cancer
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PPAR GAMMA Agonist in combination with BCR/ABL TKI in patients of CML-CP with suboptimal molecular response
December 20, 2016, Annals of Oncology

Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction
March 2016,  Journal of Phamacology and Pharmaco therapeutics   ​WARNING
​
An Antidiabetic Medication For Curing Chronic Myeloid Leukemia
January 25, 2016, Richard Béliveau

Pioglitazone, Other TZDs May Add Benefit to TKI Therapy in CML
January 11, 2016, Cancer Network

PPARγ ligands increase antileukemic activity of second- and third-generation tyrosine kinase inhibitors in chronic myeloid leukemia cells
January 8, 2016, Nature

Teaching an Old Dog New Tricks: Eradication of Leukemia Stem Cells
December 2015, ASH Publications

PPARγ: Welcoming the New Kid on the CML Stem Cell Block
October 12, 2015,  Cancer Cell

Pioglitazone purges quiescent CML stem cells
September 17, 2015, Nature

Adding pioglitazone to imatinib may improve treatment of chronic myeloid leukemia
September 9, 2015, Oncology Nurse Advisor

Adding Glitazone to Chemotherapy May Help Treat Chronic Myeloid Leukemia
September 3, 2015, Cancer Therapy Advisor

Diabetes drug may help in leukaemia
September 3, 2015, BBC News

Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists
September 2, 2015, Journal Nature

Could Common Diabetes Drugs Help Fight Leukemia?
September 2, 2015, WebMD

Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy
March 2014, Heamatologica

Targeting STAT5 Expression Resulted in Molecular Response Improvement in Patients with Chronic Phase CML Treated with Imatinib
2012,  Journal Blood

The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study            WARNING
​April 18, 2012, thebmj
​
Pioglitazone Inhibits Platelet Function and Potentiates the Effects of Aspirin       WARNING
​​November 18, 2011, Journal Blood

Diabetes drug pioglitazone (Actos): risk of fracture  WARNING
Septembre 27, 2007, NCBI

Pioglitazone inhibits the growth of human leukemia cell lines and primary leukemia cells while sparing normal hematopoietic stem cells
August  29, 2006, PubMed

Pioglitazone Ameliorates Insulin Resistance and Diabetes by Both Adiponectin-dependent and -independent Pathways
 March 31, 2006, Journal of Biological Chemistry
​
Treating type 2 diabetes in renal insufficiency: the role of pioglitazone
October 2003, PubMed
                        
                                      
                                                See also Dr. Philippe Rousselot  
                                   See also Dr. Stéphane Prost  

                                   See also Living with CML and diabètes
           See also  Inhibition of STAT5 in conjunction with standard TKI therapy  

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