搜索结果：Leukemia research

Multidrug resistance (MDR) remains a major obstacle in the clinical treatment of leukemia, severely limiting therapeutic efficacy and leading to poor patient outcomes. Drug efflux mediated by ATP-binding cassette (ABC) transporters represents a central mechanism driving cancer MDR. In this study, we identified ABCB6 as a critical mediator of MDR in leukemia through its role in promoting drug efflux. Using membrane-focused liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) analysis of the leukemia cell line K562 and its MDR derivative K562/A02, we screened for differentially expressed transporters and identified ABCB6 as a candidate molecule. We further confirmed that ABCB6 is abundantly expressed on the plasma membrane of K562/A02 cells. Functional analyses demonstrated that altered ABCB6 expression did not significantly affect cell proliferation or apoptosis; however, targeted knockdown of ABCB6 markedly restored the sensitivity of K562/A02 cells to adriamycin (ADR) and cytosine arabinoside (Ara-C). Mechanistic studies revealed that ABCB6 contributes to ADR efflux from leukemia cells, thereby reducing intracellular drug accumulation and weakening its cytotoxic activity. Together, these findings establish ABCB6 as a previously unrecognized efflux transporter that contributes to MDR in leukemia and highlight ABCB6 as a potential therapeutic target for overcoming MDR.

T-cell acute lymphoblastic leukemia (T-ALL) and chronic myelogenous leukemia (CML) are hematological malignancies arising from lymphoid and myeloid lineages, respectively. Although many patients achieve remission following chemotherapy, relapse and chemoresistance remain major clinical challenges. Sigma receptors, including sigma-1 (S1R) and sigma-2 (S2R), regulate pathways involved in cancer cell survival, stress responses, and cell death. While S2R is frequently overexpressed in tumors, S1R promotes protective mechanisms that support cancer cell survival, suggesting that dual targeting of these receptors may enhance anticancer efficacy. Siramesine (LU28-719), a selective S2R agonist originally developed for depression and anxiety disorders, has emerged as a potential anticancer agent. Using Jurkat and K562 cell lines representing distinct hematopoietic origins, we investigated the effects of Siramesine alone and in combination with BD-1047, a selective S1R antagonist, on cell viability, apoptosis, cell cycle progression, and the expression of sigma receptors, phospho-p53/p53, apoptosis-related proteins, and autophagy markers. Siramesine significantly reduced cell viability and induced apoptosis in both cell lines. These effects were associated with increased expression of S2R, phospho-p53/p53, apoptotic markers (Bax and cleaved caspase-8), and autophagy-related proteins (SQSTM1/p62 and LC3B-II). Co-treatment with BD-1047 further enhanced Siramesine-induced cell death, apoptosis, and alterations in autophagic signaling. These findings demonstrate that S1R inhibition sensitizes leukemia cells to S2R-mediated cytotoxicity, supporting the therapeutic potential of combined sigma receptor targeting and warranting further investigation of Siramesine-based metronomic therapy in leukemia.

Around 70s decade, the discovery of endoplasmic reticulum (ER) chaperones as central regulators of protein folding and quality control set a new paradigm for the understanding of cellular homeostasis. With the arrival of global proteomic approaches, several ER chaperones, including the 78-kDa glucose-regulated protein (GRP78), were unexpectedly found at the cell surface of cancer cells, linking activation of the unfolded protein response (UPR) to tumor biology. Current knowledge suggests that cell surface GRP78 (csGRP78) is a promising therapeutic biomarker, as it is virtually absent on normal cells but enriched on multiple cancers, particularly leukemias. This review summarizes the roles of the three main UPR regulators-IRE1, ATF6, and PERK-and their crosstalk with csGRP78 in leukemia, emphasizing how this network can promote survival or apoptosis. Finally, recent preclinical studies using GRP78-directed CAR-T cells are discussed, highlighting csGRP78 and the UPR pathway as attractive targets for leukemia immunotherapy.

N7-methylguanosine (m7G), a prevalent modification in tRNAs, is primarily catalyzed by the methyltransferase METTL1. While growing evidence supports a role for METTL1 in various tumors, its therapeutic potential and precise function in leukemia stem cell (LSC) homeostasis remain largely unexplored. Here, we identify METTL1 as a key regulator of LSC self-renewal and homing within bone marrow (BM) microenvironment through catalyzing m7G formation on a specific tRNA, tRNAPheGAA, thereby driving leukemogenesis. Mechanistically, METTL1 loss significantly reduces m7G abundance and steady-state levels of tRNAPheGAA, leading to translation suppression and degradation of transcripts enriched with tRNAPheGAA-related codons, such as tyrosine-protein kinase HCK. Decreased HCK expression disrupts CXCR4 signaling, impairing LSC self-renewal and BM homing. Therapeutically, we characterize a small-molecule METTL1 inhibitor (M1i; NSC137443), through high throughput screening. Pharmacological inhibition of METTL1 demonstrates potent anti-tumor efficacy by reduction of tRNA m7G levels and disrupting the tRNAPheGAA/HCK/CXCR4 cascade. Notably, targeting METTL1 significantly reduces LSC frequency, delays leukemogenesis, and prolongs survival in multiple acute myeloid leukemia models. Our findings establish a previously unrecognized role for METTL1 and its target tRNAPheGAA in LSC homeostasis and provide compelling proof-of-concept evidence that METTL1 is a druggable epitranscriptomic target for anti-leukemia therapy.

Myelodysplastic neoplasms (MDSs) are clonal hematopoietic stem cell disorders that progress to acute myeloid leukemia (AML) in 25%-30% of patients, typically over many years. Rapid transformation and central nervous system (CNS) involvement at AML diagnosis are uncommon in adults and confer a poor prognosis. We report a 35-year-old man with MDS who progressed to AML within 8 months and presented with extreme hyperleukocytosis, pulmonary infiltrates, leukemic retinopathy, and acute neuropsychiatric symptoms. Flow cytometry demonstrated nonmonocytic AML with aberrant CD7 expression and co-expression of CD34 and CD123. Next-generation sequencing revealed RUNX1 and ZRSR2 mutations defining AML with myelodysplasia-related features, with DNMT3A and TET2 mutations indicating evolution from an antecedent clone. Brain magnetic resonance imaging showed diffuse pachymeningeal enhancement, and cerebrospinal fluid confirmed CNS leukemia. Despite standard induction and intrathecal chemotherapy, bone marrow assessment demonstrated primary refractory disease. This case highlights aggressive secondary AML with adverse biology, CNS involvement, and induction failure. RésuméLes néoplasmes myélodysplasiques (NMD) sont des affections clonales des cellules souches hématopoïétiques qui évoluent vers une leucémie aiguë myéloïde (LAM) chez 25 à 30 % des patients, généralement après plusieurs années. La transformation rapide et l’atteinte du système nerveux central (SNC) au moment du diagnostic de LAM sont rares chez l’adulte et confèrent un pronostic défavorable. Nous rapportons le cas d’un homme de 35 ans atteint d’un NMD ayant évolué vers une LAM en 8 mois, avec hyperleucocytose extrême, infiltrats pulmonaires, rétinopathie leucémique et symptômes neuropsychiatriques aigus. La cytométrie en flux a mis en évidence une LAM non monocytaire avec expression aberrante de CD7 et co-expression de CD34 et CD123. Le séquençage de nouvelle génération a révélé des mutations RUNX1 et ZRSR2 définissant une LAM avec caractéristiques liées à la myélodysplasie, ainsi que des mutations DNMT3A et TET2 indiquant une évolution à partir d’un clone antécédent. L’imagerie par résonance magnétique cérébrale a montré un rehaussement pachyméningé diffus, et l’analyse du liquide céphalorachidien a confirmé une leucémie du SNC. Malgré une chimiothérapie d’induction standard et intrathécale, l’évaluation médullaire a démontré une maladie réfractaire primaire. Ce cas illustre une LAM secondaire agressive associée à une biologie défavorable, à une atteinte du SNC et à un échec d’induction.

Pancreaticoduodenectomy (PD) for ampullary carcinoma carries significant risks, and the presence of hematologic comorbidities adds further complexity. While stable Chronic Lymphocytic Leukemia (CLL) is not a contraindication, it complicates perioperative risk stratification and infection control. A 66-year-old male with type 2 diabetes mellitus (DM) and stable, untreated Rai Stage I chronic lymphocytic leukemia (CLL) presented with a three-week history of painless obstructive jaundice. Imaging and biopsy confirmed ampullary carcinoma. Following multidisciplinary team (MDT) optimization focusing on glycemic control (target 140-180 mg/dL), preoperative biliary drainage, infection prophylaxis, and immunologic surveillance, a pylorus-preserving PD (PPPD) was performed. The postoperative course was stable with no biochemical leak or clinically relevant postoperative pancreatic fistula (POPF). Histopathology revealed pT2N0 (Stage I) ampullary carcinoma (intestinal-type) with focal lymphovascular invasion (LVI). Interestingly, regional lymph nodes showed CLL infiltration but were negative for metastasis. This case shows that structured MDT optimization and adherence to ERAS protocols enabled safe curative-intent PD in this patient with stable CLL and DM.

Bovine leukemia virus (BLV) is among the most prevalent infectious diseases of dairy cattle, with herd-level infection rates exceeding 80% in many regions worldwide. While only a minority of infected animals develop clinical enzootic bovine leukosis, subclinical effects are widespread and extend beyond animal health. This narrative review examines BLV through a One Health lens, emphasizing its nutritional, food security, and public health dimensions. Relevant literature was identified through targeted searches of major scientific databases using terms related to BLV, milk composition, nutrition, food security, and One Health. Evidence suggests that BLV infection reduces milk yield and alters composition, particularly in cows with high proviral load. Decreases in fat, protein, and bioactive components diminish milk's caloric density and functional quality, potentially lowering consumers' dietary intake of essential fatty acids, fat-soluble vitamins, and immunomodulatory proteins. Increased susceptibility to mastitis due to BLV-associated immune dysfunction further exacerbates nutrient losses, compounding inefficiencies in milk production. Collectively, these changes undermine dairy's nutritional value, especially for populations that rely heavily on milk as a staple food, including young children, low-income households, and communities in low- and middle-income countries where dairy products may provide important dietary energy, protein, and micronutrients. At the systems level, BLV contributes to economic inefficiency through reduced herd productivity. These losses aggregate into a significant drag on dairy supply, with implications for affordability, accessibility, and environmental sustainability. Although definitive evidence of zoonotic transmission is lacking, recurring detection of BLV DNA, proteins, and antibodies in human tissue raises questions regarding potential public health risks. Taken together, BLV represents an underappreciated One Health challenge, encompassing animal productivity, human nutrition, economic access, and possible zoonotic implications. Future research should quantify BLV's economic and nutritional impacts on consumers and clarify risks to human health to support interventions aligned with animal health, food security, and sustainable nutrition.

Chronic myelomonocytic leukemia (CMML) is defined as a clonal disorder of the myeloid cell lineage, with the characteristic feature being monocytosis. Chromosomal abnormalities are common, but translocations involving chromosome 1p36 are rare. Here, we document a case of CMML that carried an unreported translocation involving t(1;3)(p36.2;p12). The patient showed rapid progression and died within six days post-diagnosis. The 1p36.2 chromosomal region harbors tumor suppressors such as PR domain containing 16 (PRDM16), Tumor Protein 73 (TP73), Cadherin 5 or VE-cadherin (CHD5), and Kinase Family Member 1B (KIF1B), while the 3p12 chromosomal location plays a role in the malignant transformation and disruption of the tumor suppressors, focusing on the genomic instability observed in the case. These changes may partially harbor the capacity to contribute to the pathogenesis of aggressive behaviors in leukemia through failure of apoptosis, chromatin remodeling pathways, and enhanced self-renewal capabilities of stem cells.

An integrated transcriptomic and survival analysis led to the identification of SYK and HDAC isoforms as age- and FLT3-dependent prognostic markers in acute myeloid leukemia (AML). Driven by the aforementioned, our research group employed a classical ligand-based hybrid pharmacophore strategy to furnish dual-target hybrid frameworks. Antitumor profiling culminated in a tractable bifunctional agent (Compound 14, dual SYK-HDAC inhibitor) endowed with substantial cell growth inhibitory effects against MV4-11 cell lines (AML cell lines harboring FLT3-ITD mutations). Compound 14 downregulated the expression levels of p-SYK and modulated the expression levels of the biomarkers associated with intracellular HDAC inhibition. Transcriptomic profiling revealed significantly suppressed lipid-associated metabolic pathways with Compound 14 treatment. Moreover, Compound 14 demonstrated an impressive pharmacokinetic profile and exerted significant antitumor efficacy in the FLT3-ITD-positive AML xenograft mouse model (approximately 80% decrease in tumor mass). Also, biochemical blood analysis and histopathological studies revealed that Compound 14 demonstrated a good safety profile.

Philadelphia chromosome-positive acute lymphoblastic leukemia (-Ph+ ALL) is a high-risk leukemia often accompanied by additional genomic abnormalities beyond BCR::ABL1. We analyzed 74 newly diagnosed adult -Ph+ ALL patients. Additional chromosomal abnormalities (ACAs) were assessed by conventional cytogenetics in 51 patients and copy number variations (CNVs) by combined array comparative genomic hybridization plus single nucleotide polymorphism (array-CGH+SNP) in 43 patients. ACAs were detected in 31 cases (60.8%), including complex karyotypes in 11 (35.5%). CNVs were identified in 38 cases (88.4%) and were predominantly deletions (69.2%). Recurrent abnormalities included double Ph chromosome, monosomy 7, chromosomal gains at 8q, 9q34, 22q11, and losses at 7p, 9p, and 20q. The t(3;9;22) was the most frequent t(9;22) variant (12.9%), despite being rare in previous studies of adult Ph+ ALL. IKZF1 deletions were most frequent (91.7%), followed by CDKN2A/B (44.4%), PAX5 (38.9%) and RB1 (30.6%). IKZF1 co-deletions with CDKN2A/B and/or PAX5 occurred in 66.7%. IKZF1 and 22q11.22 co-deletions occurred in 34.2%, and VPREB1 deletions in 15.8%; both have been associated with adverse outcomes in ALL. Copy-neutral loss of heterozygosity >5 Mb was detected in 16.3%, frequently involving chromosome 9p and encompassing the CDKN2A/B loci. Adult Ph+ ALL in this multi-ethnic cohort exhibited marked genomic heterogeneity, with frequent submicroscopic alterations detectable only through integrated genomic profiling. Comprehensive genomic characterization is needed to better understand leukemogenesis and refine risk stratification.

Drug resistance is a major challenge in cancer therapy, especially in hematologic malignancies where kinase inhibitors have transformed treatment yet are frequently undermined by drug resistance. While targeted protein degradation (TPD) offers a mechanistically distinct mode of action compared to inhibition-based therapeutic therapies, the potential value of TPD in drug-resistant blood cancer remains unclear. Here, we report the discovery of cereblon-recruiting molecular glue degraders (MGDs) targeting LCK, an oncogenic kinase in T-cell acute lymphoblastic leukemia (T-ALL). By high-throughput screening and medicinal chemistry optimization, we developed a series of MGDs that induced CRBN-dependent degradation of LCK as well as potent cytotoxicity in T-ALL in vitro. Structure-activity relationship analysis and ternary complex modeling revealed a non-canonical degron at the LCK-CRBN interface involving the G-loop, whose mutation disrupts this interaction. Unlike inhibitors and inhibitor-based PROTACs, these MGDs engage LCK in regions distal to the ATP binding site and thus their activities in T-ALL are not affected by gate-keeper LCK mutations that drive resistance to inhibitor-based therapeutics. Taken together, our data highlights the potential of LCK-targeting MGDs as a strategy to overcome kinase inhibitor resistance in T-ALL, offering a framework for targeting kinase dependencies in drug-refractory hematologic malignancies more broadly.

Mucormycosis, a fungal infection, usually involves the rhino-orbital-cerebral cavities in immunocompromised patients. The upper limb is one of the most infrequent sites for mucormycosis infection. We present a rare and atypical case of upper limb mucormycosis in an immunocompromised patient undergoing chemotherapy for acute lymphoblastic leukemia. The diagnosis was confirmed through histopathological examination. Prompt and aggressive intervention - including extensive surgical debridement and intravenous antifungal therapy - led to the successful preservation of both the patient's life and limb. This case is notable for successful limb salvage without amputation, despite deep tissue involvement. Prompt recognition, early surgical intervention, and appropriate antifungal therapy were key to the favorable outcome. Considering mucormycosis in immunocompromised patients, along with early diagnostic workup, biopsy, specific fungal cultures (when available), antifungal therapy, and timely surgical intervention, can lead to limb and life salvage. The present study has revealed the importance of early diagnosis and management of uncommon site infections with mucormycosis in immunocompromised individuals, particularly in hematologic malignancies.

Current treatments of T-cell acute lymphoblastic leukemia (T-ALL) are based on intensive chemotherapy regimens which provide overall survival rates of ~85% in children and <50% in adults. Therefore, there is an unmet need for novel therapeutic options in T-ALL. Pre-clinical studies and clinical trials have demonstrated that inhibitors of BCL-XL and/or BCL-2, two anti-apoptotic proteins of the BCL-2 family, are anti-leukemic in T-ALL. However, BCL-XL inhibitors (BCL-XLi) efficacy is undermined by severe, on-target thrombocytopenia. We report here the design of a novel anti-hCD7 mAb-based ADC carrying a BCL-XL-selective inhibitor (ADC-CD7-BCL-XLi) that circumvents this significant limitation. We show that ADC-CD7-BCL-XLi efficiently kills most T-ALL cell lines. Using T-ALL PDXs we further show that (i) ADC-CD7-BCL-XLi displays potent anti-leukemic activity and is devoid of toxicity to platelets; (ii) ADC-CD7-BCL-XLi acts synergistically with venetoclax, a BCL-2 selective antagonist, to prolong leukemia remission and mouse survival; (iii) the anti-leukemic effect of the ADC-CD7-BCL-XLi+venetoclax combination can lead to cure when combined with chemotherapy. These pre-clinical data strongly support the evaluation of ADC-CD7-BCL-XLi in T-ALL patients, including as a potential bridging option to curative hematopoietic stem cell transplantation (HSCT).

A 41-year-old man developed three distinct primary malignancies-acute myeloid leukemia, male breast cancer, and metastatic colorectal cancer-within 7&#x2009;years. This rare case highlights the evolving challenge of multiple primary cancers and demonstrates how coordinated multidisciplinary care can preserve curative intent despite successive life-threatening diagnoses.

Venetoclax (VEN) combined with azacitidine (AZA) or low-dose cytarabine (LDAC) has significantly improved outcomes for older patients with acute myeloid leukemia (AML). However, severe cytopenia often leads to treatment interruptions. Previous literature has reported that Asian patients tend to have higher plasma VEN concentrations and are more prone to severe neutropenia. We hypothesized that VEN pharmacokinetics (PK) influence these adverse events in the Japanese population. In a prospective observational study (UMIN000047371) involving 76 patients, we monitored VEN PK (trough, maximum plasma concentration, and area under the plasma concentration-time curve from 0 to 12 hours [AUC0-12]). Our analysis of an 81-sample PK data set revealed that samples taken 6 hours after VEN dose offered the best correlation to AUC0-12 (r = 0.945). Importantly, in patients who achieved composite complete remission, a positive correlation was found between the duration of grade 3 neutropenia and VEN AUC0-12 (r = 0.338; P = .028). We further investigated potential factors influencing VEN PK and neutropenia, specifically considering tumor burden and renal function. Samples from patients with pretreatment white blood cell (WBC) counts of <3000/&#x3bc;L and an estimated glomerular filtration rate (eGFR) of <60 mL/min exhibited significantly higher VEN AUC0-12 levels (P = .037) than other groups. These patients also demonstrated a significantly more extended period of grade 3 neutropenia (P = .037). These results suggest that VEN PK could be crucial for predicting neutrophil recovery after VEN-containing regimens in AML. Specifically, patients with low pretreatment WBC counts and low eGFR may represent a risk factor for higher VEN concentrations and, consequently, prolonged neutropenia.

Activating mutations in NOTCH1 are frequent in T-cell acute lymphoblastic leukemia (T-ALL) and, in the absence of alterations in RAS or PTEN, are associated with favorable prognosis. Besides classical heterodimerization and PEST domain mutations, juxtamembrane internal tandem duplications (JME-ITDs) represent a third class of activating variants. Their intermediate size and sequence composition can challenge short-read next-generation sequencing and variant calling algorithms, leading to underdetection in routine diagnostics. An index case of newly diagnosed T-ALL harboring a NOTCH1 juxtamembrane insertion that was discordantly detected by variant callers during routine targeted NGS (Hematology OncoKitDx v2) prompted further analysis. The variant was evaluated using VarDict and VarScan2, followed by manual inspection with IGV and orthogonal confirmation by Sanger sequencing. To further assess variability in the detection of JME-ITDs, six additional BAM files from patients with previously confirmed variants were reanalyzed using VarDict, VarScan2, Mutect2, and Pindel. In the index case, VarDict detected a 51-bp NOTCH1 JME-ITD (c.5168-2_5216dup) that was missed by VarScan2 and confirmed by Sanger sequencing. Reanalysis of the seven cases showed that Mutect2 and VarDict detected all JME-ITDs (100%), VarScan2 identified only three (42.8%), and Pindel detected six mutations (85.7%). These results reflect differences in algorithmic strategies where haplotype-based callers incorporate soft-clipped and split reads, whereas pileup-based discard them. Detection of NOTCH1 JME-ITDs depends strongly on variant-calling strategy. Combining haplotype-based callers with split-read structural variant tools may reduce false negatives and improve detection of clinically relevant insertions in diagnostic NGS pipelines.

This case describes a child with T-cell acute lymphoblastic leukemia (T-ALL) presenting atypically with ascites and bilateral pedal edema, initially suggesting autoimmune hepatitis. The diagnosis was established only after flow cytometry of ascitic fluid. It underscores that pediatric malignancies may present atypically and highlights the importance of a broad, flexible diagnostic approach to avoid delays in life-saving treatment.

Patients with acute myeloid leukemia (AML) experience severe, co-occurring, and fluctuating symptoms during treatment. Accurate identification is critical but often limited by under documentation and unstructured electronic health record notes. To develop and validate a natural language processing (NLP) system to extract symptoms from inpatient clinical notes, characterize prevalence and co-occurrence of documented symptoms, and examine whether documentation patterns vary by patient- and note-level factors. We analyzed 78,392 clinical notes from 812 AML patients admitted between 2006 and 2021. Ten symptom categories were defined (pain, gastrointestinal, myelosuppression, cardiopulmonary, skin, fatigue, anxiety/anger, central nervous system, depression, and sleep). The NLP system was validated against 240 manually annotated notes, with performance assessed by precision, recall, and F1 score. Exploratory analyses using generalized estimating equations estimated odds of documentation by sex, age, and author type. The NLP system achieved high performance across all symptom categories (average F1 = 0.90). Gastrointestinal (97.3%), pain (95.9%), and myelosuppression (95.7%) were most frequently documented, with extensive co-occurrence across encounters. Fatigue and depression were less common. Men had lower odds of depression documentation than women, and older patients had lower odds across multiple domains. Compared with physicians, advanced practice registered nurses more often documented cardiopulmonary symptoms, while other provider groups documented fewer symptoms overall. NLP enables accurate, scalable extraction of symptom data from unstructured notes, supporting large-scale surveillance and predictive modeling in AML. Findings highlight the need for standardized documentation and tailored interventions to address symptom risks across patient groups.

Tyrosine kinase inhibitors (TKIs) have transformed the treatment of chronic myeloid leukemia (CML); yet, diverse molecular responses and resistance persist. BCR::ABL1 kinase-domain (TKD) mutations constitute just a fraction of this resistance, and the impact of additional somatic mutations on disease progression and early molecular response remains incompletely defined. This single-centre cohort study analyzed 109 NGS-tested patients with CML, comprising 44 with TKI-resistant disease and 65 newly diagnosed patients. Targeted next-generation sequencing using a 135-gene myeloid panel was performed on 109 patients. An additional pilot subgroup of 30 TKI-resistant patients underwent BCR::ABL1 kinase-domain analysis by PCR/Sanger sequencing and was analyzed separately. Molecular response was assessed using BCR::ABL1 transcript levels on the International Scale and interpreted according to ELN 2020 recommendations. Somatic mutations were identified in 52.3% of TKI-resistant and 29.2% of newly diagnosed patients. All Cohort 1 blast-crisis patients were mutation-positive, and several concurrent abnormalities were more common in Cohort 1 than in Cohort 2, indicating clonal complexity. In Cohort 2, MMR was achieved in 28/39 (71.8%) mutation-negative and 6/13 (46.2%) mutation-positive patients. Mutation-positivity at baseline was associated with reduced MMR chances but not statistically significant (odds ratio 0.34; 95% confidence interval 0.09-1.23; p&#x2009;=&#x2009;0.099). ASXL1 emerged as the most common non-ABL1 mutation but was not statistically significant. In this Indian CML cohort, somatic mutations were prevalent in TKI-resistant disease, linked to advanced phase and clonal complexity, and demonstrated a non-significant trend toward lower early MMR at diagnosis, highlighting the importance of genomic testing in this context.