# Is asciminib an effective tyrosine kinase inhibitor for chronic myeloid leukemia patients with tyrosine kinase inhibitor resistance?

**Authors:** Musab MA Omar, Majed A Alanazi, Denise E. Jackson

PMC · DOI: 10.1016/j.htct.2026.106257 · Hematology, Transfusion and Cell Therapy · 2026-02-22

## TL;DR

Asciminib is a new tyrosine kinase inhibitor that offers a safer and more effective treatment for chronic myeloid leukemia patients resistant to other drugs.

## Contribution

Asciminib introduces a novel mechanism by targeting the ABL1 myristoyl pocket, offering a new treatment option for resistant patients.

## Key findings

- Asciminib has a superior safety profile with fewer cardiovascular adverse events.
- It can overcome resistance when combined with other tyrosine kinase inhibitors.
- Ongoing research is needed to improve its efficacy and manage side effects.

## Abstract

Asciminib represents a significant advancement in the treatment of chronic myeloid leukemia, establishing a novel therapeutic paradigm by specifically targeting the ABL1 myristoyl pocket, a mechanism distinct from that of conventional adenosine triphosphate-competitive inhibitors. Such a selective inhibitor offers an alternative treatment strategy for patients with chronic myeloid leukemia who have developed resistance to previous tyrosine kinase inhibitor therapies. Although asciminib demonstrates a superior safety profile, primarily characterized by a reduction in cardiovascular adverse events associated with prior tyrosine kinase inhibitors, its clinical significance extends further. The effectiveness of asciminib, combined with its capacity to overcome resistance through combination strategies with adenosine triphosphate-binding site tyrosine kinase inhibitors, establishes it as a focal point in emerging chronic myeloid leukemia treatment approaches. It remains essential to continue research and clinical trials to enhance the therapeutic efficacy of asciminib and manage its associated side effects.

## Linked entities

- **Genes:** ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25]
- **Chemicals:** asciminib (PubChem CID 72165228)
- **Diseases:** chronic myeloid leukemia (MONDO:0011996)

## Full-text entities

- **Genes:** ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase) [NCBI Gene 27] {aka ABLL, ARG}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, BCR (BCR activator of RhoGEF and GTPase) [NCBI Gene 613] {aka ALL, BCR1, CML, D22S11, D22S662, PHL}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, TTLL5 (tubulin tyrosine ligase like 5) [NCBI Gene 23093] {aka CORD19, KIAA0998, STAMP}
- **Diseases:** fluid retention (MESH:D016055), leukemia (MESH:D007938), death (MESH:D003643), neutropenia (MESH:D009503), arterial occlusive disorders (MESH:D001157), hypertension (MESH:D006973), cytopenia (MESH:D006402), thrombotic (MESH:D013927), cramps (MESH:D009120), anemia (MESH:D000740), pancreatitis (MESH:D010195), CML (MESH:D015464), toxicities (MESH:D064420), cancer (MESH:D009369), thrombocytopenia (MESH:D013921), gastrointestinal disturbances (MESH:D005767), cardiovascular adverse (MESH:D002318), CP (MESH:D002972), diarrhea (MESH:D003967), vascular complications (MESH:D003925), fatigue (MESH:D005221), liver function abnormalities (MESH:D056486), musculoskeletal pain (MESH:D059352), splenomegaly (MESH:D013163), pleural effusions (MESH:D010996), rash (MESH:D005076), pulmonary hypertension (MESH:D006976), Philadelphia (MESH:D010677), QT prolongation (MESH:D008133), hematologic malignancies (MESH:D019337)
- **Chemicals:** Ponatinib (MESH:C545373), GNF-2 (-), carbon (MESH:D002244), Asciminib (MESH:C000621806), dasatinib (MESH:D000069439), nilotinib (MESH:C498826), imatinib (MESH:D000068877), ATP (MESH:D000255), piperidine (MESH:C032727), pyrimidine (MESH:C030986), bosutinib (MESH:C471992)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** P465S, V468F, T315I, I502L, A337V
- **Cell lines:** Ba/F3 — Mus musculus (Mouse), Factor-dependent cell line (CVCL_0161)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936483/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936483/full.md

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Source: https://tomesphere.com/paper/PMC12936483