ABCB1 as a potential beneficial target of midostaurin in acute myeloid leukemia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F22%3A10445705" target="_blank" >RIV/00216208:11160/22:10445705 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/22:10445705

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FlGPb4Z67e" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FlGPb4Z67e</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biopha.2022.112962" target="_blank" >10.1016/j.biopha.2022.112962</a>

Result language

angličtina

Original language name

ABCB1 as a potential beneficial target of midostaurin in acute myeloid leukemia

Original language description

Low curability of patients diagnosed with acute myeloid leukemia (AML) must be seen as a call for better understanding the disease&apos;s mechanisms and improving the treatment strategy. Therapeutic outcome of the crucial anthracycline-based induction therapy often can be compromised by a resistant phenotype associated with overexpression of ABCB1 transporters. Here, we evaluated clinical relevance of ABCB1 in a context of the FMSlike tyrosine kinase 3 (FLT3) inhibitor midostaurin in a set of 28 primary AML samples. ABCB1 gene expression was absolutely quantified, confirming its association with CD34 positivity, adverse cytogenetic risk, and unachieved complete remission (CR). Midostaurin, identified as an ABCB1 inhibitor, increased anthracycline accumulation in peripheral blood mononuclear cells (PBMC) of CD34+ AML patients and those not achieving CR. This effect was independent of FLT3 mutation, indicating even FLT3- AML patients might benefit from midostaurin therapy. In line with these data, midostaurin potentiated proapoptotic processes in ABCB1overexpressing leukemic cells when combined with anthracyclines. Furthermore, we report a direct linkage of miR-9 to ABCB1 efflux activity in the PBMC and propose miR-9 as a useful prognostic marker in AML. Overall, we highlight the therapeutic value of midostaurin as more than just a FLT3 inhibitor, suggesting its maximal therapeutic outcomes might be very sensitive to proper timing and well-optimized dosage schemes based upon patient&apos;s characteristics, such as CD34 positivity and ABCB1 activity. Moreover, we suggest miR-9 as a predictive ABCB1-related biomarker that could be immensely helpful in identifying ABCB1-resistant AML phenotype to enable optimized therapeutic regimen and improved treatment outcome.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Efficiency and safety improvement of current drugs and nutraceuticals: advanced methods - new challenges</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomedicine &amp; Pharmacotherapy

ISSN

0753-3322

e-ISSN

1950-6007

Volume of the periodical

150

Issue of the periodical within the volume

June

Country of publishing house

FR - FRANCE

Number of pages

10

Pages from-to

112962

UT code for WoS article

000793662700001

EID of the result in the Scopus database

2-s2.0-85128970508