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Pharmacological combination for leukemia treatment

Acute myeloid leukemiaAML FLT3-ITD+Cellular stressLeucemia mieloide acutaProteostatic stressTargeted therapy


The invention proposes the use of a combination of three drugs (All-Trans-Retinoic-Acid, Arsenic Trioxide and Bortezomib) to treat FLT3-ITD positive Acute Myeloid Leukemia (AML), on the basis of experimental results obtained in vitro on AML cell lines and on primary cells isolated from AML patient bearing the FLT3-ITD mutation.

Technical features

FLT3-ITD mutation causes cell protein homeostasis (proteostasis) alteration. Indeed this protein cannot be properly folded hence it accumulates in the endoplasmic reticulum causing a basal low level of stress to which leukemic cells are adapted. In vitro experiments with AML cell lines, primary cells isolated from FLT3-ITD+ patients and normal hematopoietic progenitors obtained by healthy donors, demonstrated that the combination of all-trans Retinoic Acid, Arsenic Trioxide e Bortezomib, used at low doses not harmful when each drug is used as single agent, causes levels of proteostatic and oxidative stresses resulting highly toxic for FLT3-ITD AML cells but not for healthy progenitors with a normal proteostatic balance.

Possible Applications

  • Clinical oncology and hematology, in particular for the treatment of FLT3-ITD positive Acute Myeloid Leukemia (LAM-FLT3-ITD +).


  • The combination uses low doses of each of the drugs, so as not to be harmful when each drug is used alone;
  • The proposed drugs are already approved by regulatory agencies, albeit with other indications and not in combination, making the design and application of preclinical and clinical trials faster.