Related Experiment Video

Updated: May 2, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

7.7K

A novel tescalcin-sodium/hydrogen exchange axis underlying sorafenib resistance in FLT3-ITD+ AML

Cheuk Him Man1, Stephen S Y Lam, Murphy K H Sun

  • 1Division of Haematology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.

Blood
|March 11, 2014
PubMed

Insights

Tescalcin (TESC) and Na+/H+ exchanger 1 (NHE1) activation drive sorafenib resistance in acute myeloid leukemia (AML). Inhibiting NHE1 with HMA overcomes this resistance and reduces leukemia initiation in mice.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Internal tandem duplication (ITD) of FLT3 in AML correlates with poor prognosis.
  • Sorafenib shows efficacy against refractory FLT3-ITD(+) AML but resistance develops.
  • Mechanisms underlying sorafenib resistance in AML are not fully understood.

Purpose of the Study:

  • To investigate the role of tescalcin (TESC) and Na+/H+ exchanger type-1 (NHE1) in sorafenib resistance in FLT3-ITD(+) AML.
  • To evaluate the therapeutic potential of targeting the TESC-NHE1-pHi axis.

Main Methods:

  • Assessed TESC expression in FLT3-ITD(+) AML cell lines (MOLM-13, MV4-11).
  • Utilized small-interfering RNA (siRNA) for TESC knockdown and 5-(N,N-hexamethylene) amiloride (HMA) as an NHE1 inhibitor.
  • Established sorafenib-resistant MOLM-13 cell line (M13-RE) for drug resistance studies.
  • Performed NOD/SCID mouse xenotransplantation assays with primary AML cells.

Main Results:

  • TESC was highly expressed in FLT3-ITD(+) AML cell lines; TESC knockdown reduced intracellular pH (pHi) and induced apoptosis.
  • NHE1 inhibition with HMA mimicked TESC knockdown effects and enhanced sorafenib efficacy in resistant cells.
  • HMA treatment significantly reduced leukemia initiation in vivo in a mouse xenotransplantation model.

Conclusions:

  • A TESC-NHE1-pHi axis plays a crucial role in mediating sorafenib resistance in FLT3-ITD(+) AML.
  • Targeting NHE1 with HMA represents a promising strategy to overcome sorafenib resistance and improve AML treatment outcomes.

More Related Videos

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

7.6K
Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors04:36

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors

Published on: October 17, 2025

1.1K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
2.6K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
81
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K