Malignant Transformation Research Articles

Comprehensive Assessment of the Intrinsic Pancreatic Microbiome.

We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome. Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation. Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n=20; IPMN, n=20; PDAC, n=19) and pancreatic cyst fluid (IPMN, n=30; SCA, n=10; MCN, n=10). Assessment of bacterial DNA by quantitative PCR and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were analyzed to validate findings. Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade dysplasia (LGD) and high-grade dysplasia (HGD) IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in HGD cyst fluid. Decontamination analysis using the CPTAC database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology. Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.

Abstract P50: PAX9 Activates Cell Death via Autophagic Degradation of EGFR in Oral squamous Cell Carcinoma

Abstract PAired boX 9 (PAX9) gene belongs to the PAX family and is critically essential for physiology and development. It has a significant role in maintaining squamous cell differentiation, and its downregulation is associated with tumor initiation and malignant transformation. In this study, we have analyzed the tumor suppressive potential of PAX9 by activating autophagy-dependent apoptosis in oral squamous cell carcinoma (OSCC). PAX9 overexpression inhibited cell growth and triggered apoptosis in OSCC. Moreover, PAX9 restricted orosphere formation and epithelial-mesenchymal transition in OSCC. Similarly, overexpression of PAX9 in OSCC induced autophagy activation and displayed enhanced lysosomal function in the transcriptional-dependent mechanism. Interestingly, PAX9-activated autophagy caused EGFR degradation leading to OSCC inhibition, thus establishing that PAX9 could induce lethal autophagy. In addition, PAX9 involves chemosensitizing OSCC to anticancer drugs, which exhibited profound growth inhibitory potential in OSCC. To check the status of PAX9 expression in OSCC in patient tissue, we performed IHC, and surprisingly, the expression of PAX9 was found to decreased in a higher grade of cancer tissues compared to the normal tissues. Further, we established a DMBA-induced oral carcinoma in hamster model, and it was observed that the expression of PAX9 was decreased in the 12th and 16th weeks of DMBA-exposed tissue compared to the normal tissue. On a mechanistic view, PAX9 expression was reduced with enhanced expression of DNMT1 in exposure to carcinogen in OSCC in vitro, indicating a potential association of methylation in controlling the expression of PAX9 during carcinogenesis. Citation Format: Chandra Sekhar Bhol, Gautam Sethi, Sujit Kumar Bhutia. PAX9 Activates Cell Death via Autophagic Degradation of EGFR in Oral squamous Cell Carcinoma [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P50.

Malignancy in Abdominal Wall Endometriosis: Is There a Way to Avoid It? A Systematic Review

Background: Malignant-associated abdominal wall endometriosis (AWE) is a rare pathology, likely to occur in 1% of scar endometriosis. The objectives of this study were to update the evidence on tumor degeneration arising from AWE to notify about the clinical characteristics, the different treatments offered to patients and their outcomes. Methods: A comprehensive systematic review of the literature was conducted. PubMed, Embase and Cochrane Library databases were used. Prospero (ID number: CRD42024505274). Results: Out of the 152 studies identified, 63 were included, which involved 73 patients. The main signs and symptoms were a palpable abdominal mass (85.2%) and cyclic pelvic pain (60.6%). The size of the mass varied between 3 and 25 cm. Mean time interval from the first operation to onset of malignant transformation was 20 years. Most common cancerous histological types were clear cell and endometrioid subtypes. Most widely accepted treatment is the surgical resection of local lesions with wide margins combined with adjuvant chemotherapy. The prognosis for endometriosis-associated malignancy in abdominal wall scars is poor, with a five-year survival rate of around 40%. High rates of relapse have been reported. Conclusions: Endometrial implants in the abdominal wall should be considered as preventable complications of gynecological surgeries. Special attention should be paid to women with a history of cesarean section or uterine surgery.

Prevalence and Malignant Transformation Rate of Oral Erythroplakia Worldwide - A Systematic Review

Abstract Background: To determine the characteristics of oral erythroplakia (OE) on a global scale, it is important to analyse and evaluate findings from various studies conducted across multiple geographical locations. Objectives: This review was conducted to determine the prevalence and malignant transformation rate (MTR) of OE. Data Sources: A systematic search was performed to identify studies reporting the prevalence and MTR of OE across various databases – PubMed, Web of Science, Google Scholar, Elsevier and ScienceDirect without any restriction for the time of publication. Study Eligibility Criteria: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, and the protocol was registered in the PROSPERO database (ID: 42023395215). Results: The prevalence rate of OE reported across the studies ranged from 0.04% to 1.14% with a mean of 0.25 + 0.002%. The MTRs reported across the studies included ranged from 2.6% to 65% with a mean of 30 ± 0.2%. Limitations and Conclusions: Based on the findings from the present review, it can be concluded that while the range of MTRs of OE varies widely across different geographical locations, the average rate can be considered 30%. The review also identified a need for conducting more studies on the prevalence rates as well as longitudinal studies assessing the MTR across different regions.

Endometriosis-Associated Ovarian Cancer: From Molecular Pathologies to Clinical Relevance

Endometriosis is a chronic condition affecting reproductive-aged women, characterized by the growth of ectopic endometrial tissue. Despite being benign, endometriosis is associated with an increased risk of certain cancers, including endometriosis-associated ovarian cancer (EAOC). Ovarian cancer is rare, but more common in women with endometriosis, particularly endometrioid and clear-cell carcinomas. Factors such as hormonal imbalance, reproductive history, environmental exposures, and genetic predisposition contribute to the malignant transformation of endometriosis. Thus, understanding potential risk factors causing malignancy is crucial. Over the past few decades, various genetic mutations, microRNAs, as well as tumor microenvironmental factors have been identified, impacting pathways like PI3K/AKT/mTOR, DNA repair mechanisms, oxidative stress, and inflammation. Thus, this review aims to summarize molecular studies involved in EAOC pathogenesis as potential therapeutic targets. However, further research is needed to better understand the molecular and environmental factors driving EAOC development, to target the susceptibility of endometriotic lesions to malignant progression, and to identify effective therapeutic strategies.

Diagnostic dilemma – Ovarian dermoid cysts presenting with uncommon complications and a rare association

Mature cystic teratomas, also known as dermoid cysts, are commonly encountered ovarian tumors accounting for up to 10–25% of all ovarian neoplasms. Mostly asymptomatic and incidentally detected, they may present with associated complications such as torsion, rupture, malignant transformation, and infection. Fistulization of ovarian cysts into the bowel is a rare complication and occurs in cases of infection or malignant transformation. We present a rare case of an infected dermoid cyst with co-existing endometriosis and fistulization into the rectum in a 35-year-old female. The patient presented with fever, pain, and history of infertility. This article highlights the important differential diagnosis to be considered in a multiloculated ovarian cyst containing fat and pockets of air.

Shaping Oncogenic Microenvironments: Contribution of Fibronectin

The extracellular matrix (ECM) is a complex network of proteins and glycans, dynamically remodeled and specifically tailored to the structure/function of each organ. The malignant transformation of cancer cells is determined by both cell intrinsic properties, such as mutations, and extrinsic variables, such as the mixture of surrounding cells in the tumor microenvironment and the biophysics of the ECM. During cancer progression, the ECM undergoes extensive remodeling, characterized by disruption of the basal lamina, vascular endothelial cell invasion, and development of fibrosis in and around the tumor cells resulting in increased tissue stiffness. This enhanced rigidity leads to aberrant mechanotransduction and further malignant transformation potentiating the de-differentiation, proliferation and invasion of tumor cells. Interestingly, this fibrotic microenvironment is primarily secreted and assembled by non-cancerous cells. Among them, the cancer-associated fibroblasts (CAFs) play a central role. CAFs massively produce fibronectin together with type I collagen. This review delves into the primary interactions and signaling pathways through which fibronectin can support tumorigenesis and metastasis, aiming to provide critical molecular insights for better therapy response prediction.

Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia.

The emergence of next generation sequencing and widespread use of mutational profiling in acute myeloid leukemia (AML) has broadened our understanding of the heterogeneous molecular basis of the disease. Since genetic sequencing has become a standard practice, several driver mutations have been identified. Accordingly, novel targeted therapeutic agents have been developed and are now approved for the treatment of subsets of patients that carry mutations in FLT3, IDH1, and IDH2 [1, 2]. The emergence of these novel agents in AML offers patients a new modality of therapy, and shifts treatment paradigmstoward individualized medicine. In this review, we outline the role of IDH mutations in malignant transformation, focus in on a novel group of targeted therapeutic agents directed toward IDH1- and IDH2-mutant AML, and explore their impact on prognosis in patients with AML.

Genome-wide DNA methylation-analysis of blastic plasmacytoid dendritic cell neoplasm identifies distinct molecular features.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES and RNA-seq as well as ATAC-seq on selected cases. We determined the BPDCN DNA methylation profile and observed a dramatic loss of DNA methylation during malignant transformation from early and mature DCs towards BPDCN. DNA methylation profiles further differentiate between BPDCN, AML, CMML, and T-ALL exhibiting the most striking global demethylation, mitotic stress, and merely localized DNA hypermethylation in BPDCN resulting in pronounced inactivation of tumor suppressor genes by comparison. DNA methylation-based analysis of the tumor microenvironment by MethylCIBERSORT yielded two, prognostically relevant clusters (IC1 and IC2) with specific cellular composition and mutational spectra. Further, the transcriptional subgroups of BPDCN (C1 and C2) differ by DNA methylation signatures in interleukin/inflammatory signaling genes but also by higher transcription factor activity of JAK-STAT and NFkB signaling in C2 in contrast to an EZH2 dependence in C1-BPDCN. Our integrative characterization of BPDCN offers novel molecular insights and potential diagnostic applications.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Incidental finding of acquired cystic kidney disease associated renal cell carcinoma in an adolescent with kidney failure.

Acquired cystic kidney disease (ACKD) can occur in patients with chronic kidney disease and kidney failure, and its incidence increases with the duration of dialysis. In adults, ACKD is less common in the pre-dialysis group (~ 7%), but its incidence can be as high as 80% for those who are on dialysis for more than ten years. There is, however, very little information about the prevalence of ACKD in children. We report a case of malignant transformation of ACKD following a kidney transplant, highlighting the importance of surveillance of the native kidneys in paediatric patients who have been in long-term kidney replacement therapy.

Ovarian Causes of Pseudomyxoma Peritonei (PMP)—A Literature Review

Background. Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing, inadequately understood neoplasm with a 5-year progression-free survival rate of as low as 48%. It is characterized by varying degrees of malignancy and the production of mucinous and gelatinous structures. Typically, the development of pseudomyxoma peritonei is associated with the rupture of appendiceal mucinous tumors and other gastrointestinal or ovarian mucinous tumors. The goal of our literature review was to identify various aspects that characterize the ovarian causes of pseudomyxoma peritonei. Materials and methods. The authors performed an extensive literature search between 1 February 2024 and 2 March 2024 on the following databases: Pubmed, Scopus, Oxford Journals, and Reaxys, and the findings were summarized into seven main clinical and paraclinical situations. Results. According to our research, the main instances in which pseudomyxoma peritonei can be triggered by an ovarian cause are the following: (1) mucinous cystadenoma; (2) mucinous ovarian cancer; (3) colon cancer with ovarian metastasis; (4) malignant transformation of an ovarian primary mature cystic teratoma; (5) appendiceal mucocele with peritoneal dissemination mimicking an ovarian tumor with peritoneal carcinomatosis; (6) mucinous borderline tumor developing inside an ovarian teratoma; and (7) the association between a mucinous bilateral ovarian cancer and a colonic tumor. Conclusions. In our study, we aimed to provide a comprehensive overview of the ovarian causes of pseudomyxoma peritonei, including its epidemiology, imagery characteristics, symptoms, current treatment, and promising future therapies, in the hopes of finding feasible solutions, as a lack of understanding of this mucus-secreting malignant disease increases the risk of delayed diagnosis or uncontrolled deterioration.

Endometriosis in Menopausal Women—A New Age Is Coming? Literature Review

Endometriosis is a chronic inflammatory disease, characterized by the presence of ectopic endometrial tissue, that leads to dysmenorrhea, painful intercourse and infertility. The shift in paradigm from the previous belief that endometriosis exclusively impacts women of reproductive age has brought attention to the condition in both premenarchal and postmenopausal women. Currently, 2–4% of postmenopausal women have endometriosis. Many women experience menopausal symptoms during the peri- and postmenopausal periods and require extensive investigations and monitoring in order to avoid the recurrence of endometriosis symptoms or the risk of malignant transformation when treatment with menopausal hormones is elected. Our goal was to compile and present a clear and concise overview of the existing literature on postmenopausal endometriosis, offering an up-to-date and precise summary of the available information.

Current Concepts in the Treatment of Giant Cell Tumor of Bone: An Update

Curettage is recommended for the treatment of Campanacci stages 1–2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1–3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB.

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

AbstractEnergy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease).The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches.Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles—all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large.

Mechanisms of sexual dimorphism in the pathogenesis of sarcomas

Sarcomas of non-genital organs affect women 1.5–3 times less often than men. The mechanism of such dimorphism is studied at various levels, mainly in the field of influence on the pathogenesis of sex hormones and their receptors, the effect of which is significantly related to the histogenesis of the tumor, its localization, the mechanism of malignant transformation and the stage of progression. Sex hormone receptors are often found in the early stages of tumor development and are lost during progression. At the same time, the expression of the same receptors in tumors of different histogenesis sometimes correlates with the opposite prognosis of the disease and sensitivity to hormonal therapy. For example, in uterine leiomyosarcomas, the expression of estrogen and androgen receptors correlates with a better prognosis and greater effectiveness of therapy, and in osteo- and fibrosarcomas, vice versa. Estrogens stimulate proliferation of osteosarcoma cells, and androgens that of rhabdomyosarcoma and small round cell tumor, which growth is inhibited by antiandrogens used in the treatment of prostate cancer. In this regard, when trying to include a hormonal component in a therapeutic complex, an individual study of the hormonal sensitivity of the tumor is necessary. One of the methodological approaches to this could be testing a culture of tumor cells from surgical material for sensitivity to agonists/antagonists of hormonal receptors separately and in combination with chemotherapy drugs.

Análise Radiográfica e Manejo Cirúrgico de Osteoma em Região de Ângulo Mandibular: Relato de caso

This article presents a case study of mandibular osteoma, highlighting its rarity, diagnostic challenges, and the efficacy of surgical excision as treatment. The relevance of considering osteomas in the differential diagnosis of asymptomatic mandibular masses is discussed, addressing the challenges encountered in differentiating them from other bone pathologies. The discussion emphasizes the importance of clinical history in identifying potential etiologies, especially in cases of trauma. Treatment, centered on surgical excision, is emphasized for its effectiveness, low recurrence rate, and absence of malignant transformation, contributing to a positive prognosis. This case underscores the need for a meticulous approach in the diagnosis and management of mandibular osteomas, aiming to optimize clinical outcomes.

Case Report: Leathery black plaque on the temple and scalp

Background Epidermal nevus sebaceous, commonly known as the nevus sebaceous of Jadassohn, is a congenital sebaceous hamartoma. It typically manifests as a single yellowish plaque across the head and neck and is composed of sebaceous glands. It commonly occurs during infancy and grows during puberty. Usually, it follows a benign course; however, in a few cases, it can be malignant. This is the case of a 13-year-old child with verrucous plaques on the temple and scalp. Case report We report the case of a 13-year-old boy with a steadily developing hyperpigmented verrucous plaque on the scalp and ipsilateral side of his face. A dermoscopic examination revealed ridges and fissures in a cerebriform pattern with yellowish-gray globules and a papillary appearance. Physical examination and laboratory tests revealed no abnormalities. Biopsies were taken from the scalp and temple area, and the findings were consistent with the diagnosis of nevus sebaceous. The patient was referred to a plastic surgeon for a staged excision. Conclusions We describe a unique example of a sebaceous nevus that affected the scalp and ipsilateral side of the face. As this hamartomatous growth carries the risk of cancer development, a dermatologist must identify the condition and begin treatment before malignant transformation occurs. This example of multiple verrucous plaques is an exception.

A Review of the Repair of DNA Double Strand Breaks in the Development of Oral Cancer.

We explore the possibility that defects in genes associated with the response and repair of DNA double strand breaks predispose oral potentially malignant disorders (OPMD) to undergo malignant transformation to oral squamous cell carcinoma (OSCC). Defects in the homologous recombination/Fanconi anemia (HR/FA), but not in the non-homologous end joining, causes the DNA repair pathway to appear to be consistent with features of familial conditions that are predisposed to OSCC (FA, Bloom's syndrome, Ataxia Telangiectasia); this is true for OSCC that occurs in young patients, sometimes with little/no exposure to classical risk factors. Even in Dyskeratosis Congenita, a disorder of the telomerase complex that is also predisposed to OSCC, attempts at maintaining telomere length involve a pathway with shared HR genes. Defects in the HR/FA pathway therefore appear to be pivotal in conditions that are predisposed to OSCC. There is also some evidence that abnormalities in the HR/FA pathway are associated with malignant transformation of sporadic cases OPMD and OSCC. We provide data showing overexpression of HR/FA genes in a cell-cycle-dependent manner in a series of OPMD-derived immortal keratinocyte cell lines compared to their mortal counterparts. The observations in this study argue strongly for an important role of the HA/FA DNA repair pathway in the development of OSCC.

Linc01588 deletion inhibits the malignant biological characteristics of hydroquinone-induced leukemic cells via miR-9-5p/SIRT1

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9–5p, miR-9–5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9–5p, miR-9–5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9–5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9–5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9–5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.