ABL1 (ABL proto-oncogene 1)

A bone marrow examination after two cycles confirmed the maintenance of hematological remission, and RT-PCR showed reduced minor BCR-ABL mRNA levels. AML with BCR-ABL1 fusion generally has a poor prognosis and has no established treatment, but in this case, treatment with venetoclax and azacitidine successfully induced remission and demonstrated potential efficacy against BCR-ABL fusion-positive clones.

In summary, TP53 del may serve as a predictor for poor prognosis in pediatric B-ALL. In particular, children in the intermediate-risk group with positive MRD and TP53 del may require more aggressive treatment.

P1, N=50, Recruiting, University College, London | Active, not recruiting --> Recruiting | N=38 --> 50 | Trial completion date: Dec 2036 --> Dec 2041 | Trial primary completion date: Dec 2028 --> Dec 2026

Patients with the e19a2 transcript often show poor response to first-line treatment with imatinib, and no standard therapy has been established for this subtype...Following treatment discontinuation and prednisone therapy, the patient continued dasatinib (80 mg/d)...The patient was then switched to flumatinib (600 mg/d), achieving major molecular response (MMR) at 6 months and deep complete molecular response (MR4.5) at 24 months, with good tolerance. Flumatinib demonstrated excellent deep molecular response and good tolerability in e19a2-positive CML patients, suggesting that it may be one of the preferred treatment options for such patients.

With the support of the International CML Foundation (iCMLf), which aims to improve outcomes for CML patients globally, this rare case from Brazil is discussed from the perspective of a pediatric hemato-oncologist from a high-income country, a pediatric hemato-oncologist from a low- and middle-income country, an adult CML hematologist, and the treating physician. Sharing cases of pCML in LMICs and highlighting the resources offered by the iCMLf, particularly the Knowledge Center (available online), will hopefully improve the expertise on pCML treatment worldwide.

P2, N=31, Completed, University of Campinas, Brazil | Active, not recruiting --> Completed

P=N/A, N=0, Completed, University College, London | Active, not recruiting --> Completed | N=1033 --> 0 | Trial completion date: Dec 2025 --> Feb 2025

Conversely, RB1 gene mutations were absent in all cases and no direct association between ASS1 gene deletion and imatinib treatment resistance was observed. These findings emphasize the clinical relevance of identifying additional abnormalities alongside BCR/ABL1 translocation for predicting disease progression and guiding treatment strategies in CML.

These findings suggest that resveratrol exerts anti-proliferative and pro-apoptotic effects in CML cells by modulating key genes and induction of DNA fragmentation, highlighting its potential as a therapeutic agent for CML treatment.

As the landscape of Ph-like ALL detection evolves, integrating low-cost, rapid-turnaround approaches holds significant promise for improving patient outcomes globally. This review aims to highlight the challenges and opportunities in diagnosing and treating Ph-like ALL in LMICs, fostering efforts towards more accessible and effective diagnostic strategies to enhance patient care and prognosis.

P2, N=163, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

After YAP silencing, a significant change in mRNA expression was present only in the case of ABL1. YAP mRNA expression does not significantly increase after exposure to UVB; however, it upregulates the expression of its proven (LATS1/2, JNK1/2) regulators, suggesting that in real-life settings, UV-induced dysregulation of the Hippo pathway may not be limited to YAP.

We observed that certain transcriptome features present at diagnosis persisted after 12 months of nilotinib treatment, compared to CTRLs. This suggests that nilotinib may exert selective pressure, potentially supporting the survival and self-renewal of LSCs. Future insights into these pathways could help identify therapeutic targets to improve outcomes in CML.

Furthermore, targeting SUMOylation of BCR-ABL restrained the proliferation of TKI-resistant CML cells. These results identify the mechanism by which TRIM28 maintains BCR-ABL stability to promote CML progression and suggest SUMOylation as a target for CML treatment.

In this case, a phototoxic rash that developed in a 78-year-old bcr-abl positive acute lymphoblastic leukemia patient is presented. This case supports that phototoxic reactions may occur with dasatinib and emphasizes that clinicians should be alert for this side effect.

The reporting odds ratios and their 95% confidence intervals for BCR-ABL inhibitor monotherapy, asciminib, nilotinib, and ponatinib were 1.31 (1.27-1.36), 2.11 (1.45-3.06), 2.66 (2.53-2.80), and 1.18 (1.05-1.33), respectively. Dasatinib plus triazole antifungal agents (reporting odds ratio: 2.98, 95% CI: 1.93-4.60) and ponatinib plus triazole antifungal agents (reporting odds ratio: 1.53, 95% CI: 1.08-2.16) were associated with a higher disproportionality of cardiac arrhythmias than BCR-ABL inhibitor monotherapy. The median time-to-onset was longer with monotherapy than with BCR-ABL inhibitors plus triazole antifungal agents (2.63 vs. 0.34 months, p < 0.001), both indicating an early failure type. BCR-ABL inhibitors plus triazole antifungal agents increase the risk of cardiac arrhythmia, particularly in the early stages of treatment, with the risk decreasing over time.

We can use these powerful research instruments to unravel the molecular and spatial puzzles of CML by overcoming the current obstacles. A new age of patient-centered hematology care will be ushered in by this, opening the door for improved diagnosis accuracy, sophisticated risk assessment, and customized treatment plans.

This review describes how neutrophils might contribute to the development of the inflammatory bone marrow niche, and hereby also fibrosis, associated with MPNs. The versatile functions and effects in different contexts emphasize the necessity for future research oriented to bone marrow in addition to peripheral blood.

Additionally, genetic differences were identified between paediatric and young adult BCR::ABL1-like subtypes. The extremely poor prognosis for unclassified young adults highlights the potential use of further subdivision of unfavourable genetic subtypes in refining risk classification and treatment optimization.

BK40196 inhibits c-Kit and may play an important role in peripheral and central immunity via mast cells and microglia, respectively, and induces synergistic mechanisms through anti-inflammation and protein clearance that are mutually beneficial to alleviate neurodegenerative pathology. BK40196 is a potential candidate for the treatment of human tauopathies.

P2, N=406, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2025 --> Mar 2026

P2, N=7, Terminated, M.D. Anderson Cancer Center | N=40 --> 7 | Trial completion date: Dec 2025 --> Mar 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Mar 2025; 75% < Participants, Administrativley Complete

P2, N=22, Completed, Sameek Roychowdhury | Active, not recruiting --> Completed

PTEN has been described as an essential regulator of Plk1 for dephosphorylation and chromosomal stability during cell division, and Plk1 may directly interact with and phosphorylate PTEN at centromeres. Here, we review the bidirectional interplay between Plk1 and PTEN and how it contributes to genomic stability during mitosis.

In conclusion, while CD26 + LSC are frequently observed in patients with poor molecular response, their levels significantly decrease as patients achieve DMR. However, their persistence or recurrence in TFR lacks prognostic value for molecular relapse, indicating that CD26 + LSC are not reliable predictors of outcomes in CML.

MPAL is rare and complex, with heterogeneous clinical and biological features. A literature review suggests that ALL chemotherapy is better for achieving a favorable prognosis than AML regimens.

We also identified 5 novel mutations that had not been reported in public databases which expands the spectrum of known mutations in BCR::ABL1 fusion gene. Our study also highlighted the impact on patient outcomes following the implementation of ELN guidelines underscores the importance of adherence to standardized protocols in clinical practice.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

P2, N=21, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2025 --> Feb 2026

P2, N=156, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025

Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended based on established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.

No abstract available

Moreover, we identified two PABPC1 inhibitors that inhibited BC progression and overcame TKI resistance in murine and human CML. Overall, our work identifies PABPC1 as a selective translation enhancing factor in CML-BC, with its genetic or pharmacological inhibition overcoming TKI resistance and suppressed BC progression.

P2, N=104, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P2, N=174, Completed, University of Liverpool | Unknown status --> Completed

Six BCR::ABL1 TKIs have been approved by the US Food and Drug Administration, including 5 that are first-line treatment (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and 5 approved for treatment after disease progression despite initial therapy (dasatinib, bosutinib, nilotinib, ponatinib, asciminib). Many patients require continuous TKI therapy. Therefore, TKI therapy should be selected with consideration of adverse effects, and patients should be helped to maximize adherence to TKI treatment.

Furthermore, we characterized FOS as a functionally essential downstream target of ZNF217, and ZNF217 inhibited FOS expression in a CoREST-independent manner. Our findings highlight ZNF217 as a promising therapeutic target for the treatment of high-risk B-ALL, such as those carrying MLL-rearrangements or BCR-ABL fusion.

CD19@NP/17-DMAG nanoparticles demonstrated enhanced efficacy in murine models of BCR-ABL1⁺ B-cell acute lymphoblastic leukemia (B-ALL) when combined with tyrosine kinase inhibitors (TKIs), including the BCR-ABL1-targeted imatinib and the broad-spectrum ponatinib. In addition, CD19@NP/17-DMAG was effective in another B-cell malignancy model, A20 lymphoma, significantly slowing tumor growth and amplifying T-cell responses. These findings highlight the CD19@NP/17-DMAG system as a promising therapeutic approach that both augments T cell immune responses and minimizes side effects in B-cell malignancies.

Our results provide insights into the immune microenvironment of MPNs based on immunophenotypic features and provide potential immune markers for MPNs occurrence and development.

However, indirect methods for assessing clonality limit our conclusions. Understanding clonal architecture of MPNs with co-mutations is needed to understand the underlying biology and give appropriate therapy.

Imatinib (first generation), dasatinib, nilotinib and bosutinib (second generation) and ponatinib (third generation) are the five approved TKIs that inhibit BCR::ABL1 by binding to the ATP binding site of ABL1. In this review we detail the mechanism of action, preclinical data, clinical data, safety and tolerability of asciminib. Due to its mechanism of action, asciminib has fewer off target effects, resulting in an improved safety and tolerability profile.

No abstract available