Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy.

Post-transcriptional regulation by RNA binding proteins can determine gene expression levels and drive changes in cancer cell proteomes. Identifying mechanisms of protein-RNA binding, including preferred sequence motifs bound in vivo, provides insights into protein-RNA networks and how they impact mRNA structure, function, and stability. In this review, we will focus on proteins that bind to AU-rich elements (AREs) in nascent or mature mRNA where they play roles in response to stresses encountered by cancer cells. ARE-binding proteins (ARE-BPs) specifically impact alternative splicing, stability, decay and translation, and formation of RNA-rich biomolecular condensates like cytoplasmic stress granules (SGs). For example, recent findings highlight the role of ARE-BPs - like TIAR and HUR - in chemotherapy resistance and in translational regulation of mRNAs encoding pro-inflammatory cytokines. We will discuss emerging evidence that different modes of ARE-BP activity impact leukaemia and lymphoma development, progression, adaptation to microenvironment and chemotherapy resistance.

Risk Factors for Teicoplanin-Associated Acute Kidney Injury in Patients with Hematological Malignancies: Focusing on Concomitant Use of Tazobactam/Piperacillin.

Patients with hematological malignancies (HM) often receive tazobactam/piperacillin (TAZ/PIPC) and glycopeptide antibiotics for febrile neutropenia. The effect of concomitant use of TAZ/PIPC on risk of teicoplanin (TEIC)-associated acute kidney injury (AKI) remains unclear. We investigated the impact of concomitant TAZ/PIPC use on TEIC-associated AKI in HM patients and identified the risk factors. In this retrospective, single-center, observational cohort study, 203 patients received TEIC, 176 of whom satisfied the selection criteria and were divided into TEIC cohort (no TAZ/PIPC; n = 118) and TEIC + TAZ/PIPC cohort (n = 58). AKI was defined as serum creatinine increase ≥0.3 mg/dL within 48 h or ≥50% from baseline. Incidence of AKI in TEIC cohort before and after propensity score matching was 9.3 and 5.9%, respectively, and that in TEIC + TAZ/PIPC cohort was 10.3 and 11.8%. AKI incidence and risk were not significantly different between two cohorts before (p = 0.829; odds ratio (OR) 1.122, 95% confidence interval (CI) 0.393-3.202) and after matching (p = 0.244; OR 2.133, 95% CI 0.503-9.043). Logistic regression analysis with factors clinically or mechanistically potentially related to TEIC-associated AKI, including concomitant TAZ/PIPC use, as independent variables identified baseline hemoglobin level as the only significant risk factor for TEIC-associated AKI (p = 0.011; OR 0.484, 95% CI 0.276-0.848). In HM patients treated with TEIC, concomitant TAZ/PIPC use did not increase AKI risk whereas lower hemoglobin levels had higher risk for TEIC-associated AKI development, suggesting the necessity to monitor serum creatinine when using TEIC in patients with anemia.

Clinical pharmacokinetics and pharmacodynamics of venetoclax, a selective B-cell lymphoma-2 inhibitor.

Venetoclax, a highly potent BCL-2 inhibitor, is indicated for treatment of some hematologic malignancies as monotherapy, and/or in combination with other agents. Venetoclax pharmacokinetics has been extensively characterized in patients and healthy participants. After oral dosing, the median time to reach maximum plasma concentration ranged from 5 to 8 h and harmonic mean half-life ranged from 14 to 18 h. Food increases venetoclax bioavailability by 3-5-fold and venetoclax should be administered with food to ensure adequate and consistent bioavailability. Venetoclax is eliminated via cytochrome P450 (CYP)3A metabolism, and a negligible amount of unchanged drug is excreted in urine. Strong CYP3A/P-glycoprotein inhibitors increased venetoclax exposures (AUC) by 1.44- to 6.90-fold while a significant decrease (71%) has been observed when dosed with strong CYP3 inducers. Venetoclax does not inhibit or induce CYP enzymes or transporters. Venetoclax pharmacokinetics is not appreciably altered by age, weight, sex, but the exposure is up to twofold higher in participants from Asian countries. Mild-to-severe renal impairment or end-stage renal disease do not alter venetoclax exposures, and venetoclax is not cleared by dialysis. Although mild-to-moderate hepatic impairment does not affect venetoclax exposures, twofold higher exposure was observed in subjects with severe hepatic impairment. Venetoclax exposure is comparable across patients with different hematologic malignancies and healthy participants. Overall, venetoclax exposure is only affected by food and CYP3A modulators and is only higher in Asian subjects and subjects with severe hepatic impairment. Venetoclax exposure-response relationships are malignancy-dependent and can be different between monotherapy and combination therapy.

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers.

We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with specific antibodies. Val-ILs injected intravenously rapidly reached the bone marrow and spleen, indicating their potential to effectively target cancer cells in these areas. Following the transplantation of human pediatric B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), or acute myeloid leukemia (AML) in immunodeficient NSG mice, we generated patient-derived xenograft (PDX) models, which were treated with Val-ILs loaded with antibodies to target CD19, CD7 or CD33. Only a small amount of valrubicin incorporated into Val-ILs was needed to induce leukemia cell death in vivo, suggesting that this approach could be used to efficiently treat acute leukemia cells. We also demonstrated that Val-ILs could reduce the risk of contamination of CD34+ hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation, which is a significant advantage for clinical applications. Using EL4 lymphoma cells on immunocompetent C57BL/6 mice, we also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen, which could be valuable in impairing cancer cell expansion, particularly in lymphoma cases. The most efficient Val-ILs were found to be those loaded with CD11b or CD223 antibodies, which, respectively, target the myeloid-derived suppressor cells (MDSC) or the lymphocyte-activation gene 3 (LAG-3 or CD223) on T4 lymphocytes. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.

Causes and outcomes of non-chemotherapy induced neutropenic fever in hospitalized adults: An observational study.

Neutropenic fever in adults undergoing chemotherapy for cancer treatment is a medical emergency and has been the focus of numerous studies. However, there is a paucity of data about non-chemotherapy induced neutropenic fever (non-CINF). We retrospectively reviewed 383 adults with neutropenic fever hospitalized at one academic medical center between October 2015 and September 2020 to characterize the frequency, causes, and outcomes of non-CINF. Twenty-six percent of cases of neutropenic fever were non-chemotherapy induced. Among these, the major causes of neutropenia were hematologic malignancy, infection, and rheumatologic disease, and the major causes of fever were infections. Patients with non-CINF had a higher 30-day mortality than those with chemotherapy induced neutropenic fever (25% vs 13%, P = .01). Non-CINF constituted > 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.

Homoharringtonine: updated insights into its efficacy in hematological malignancies, diverse cancers and other biomedical applications.

HHT has emerged as a notable compound in the realm of cancer treatment, particularly for hematological malignancies. Its multifaceted pharmacological properties extend beyond traditional applications, warranting an extensive review of its mechanisms and efficacy. This review aims to synthesize comprehensive insights into the efficacy of HHT in treating hematological malignancies, diverse cancers, and other biomedical applications. It focuses on elucidating the molecular mechanisms, therapeutic potential, and broader applications of HHT. A comprehensive search for peer-reviewed papers was conducted across various academic databases, including ScienceDirect, Web of Science, Scopus, American Chemical Society, Google Scholar, PubMed/MedLine, and Wiley. The review highlights HHT's diverse mechanisms of action, ranging from its role in leukemia treatment to its emerging applications in managing other cancers and various biomedical conditions. It underscores HHT's influence on cellular processes, its efficacy in clinical settings, and its potential to alter pathological pathways. HHT demonstrates significant promise in treating various hematological malignancies and cancers, offering a multifaceted approach to disease management. Its ability to impact various physiological pathways opens new avenues for therapeutic applications. This review provides a consolidated foundation for future research and clinical applications of HHT in diverse medical fields.

Determination of drug-related problems in the hematology service: a prospective interventional study.

BACKGROUND: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey. METHODS: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version. RESULTS: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033-20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125-1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%). CONCLUSIONS: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

A systematic review of the cost and cost-effectiveness of immunoglobulin treatment in patients with hematological malignancies.

OBJECTIVES: Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown. METHODS: A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies. RESULTS: Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations. CONCLUSIONS: Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.

TNF-α promoter hypomethylation is frequent in oncopediatric patients who recovered from mucositis.

The aim of this study was to investigate the DNA methylation profile in genes encoding catalase (CAT) and superoxide dismutase (SOD3) enzymes, which are involved in oxidative stress mechanisms, and in genes encoding pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-α) in the oral mucosa of oncopediatric patients treated with methotrexate (MTX®). This was a cross-sectional observational study and the population comprised healthy dental patients (n = 21) and those with hematological malignancies (n = 64) aged between 5 and 19 years. Oral conditions were evaluated using the Oral Assessment Guide and participants were divided into 4 groups: 1- healthy individuals; 2- oncopediatric patients without mucositis; 3- oncopediatric patients with mucositis; 4- oncopediatric patients who had recovered from mucositis. Methylation of DNA from oral mucosal cells was evaluated using the Methylation-Specific PCR technique (MSP). For CAT, the partially methylated profile was the most frequent and for SOD3 and IL6, the hypermethylated profile was the most frequent, with no differences between groups. For TNF-α, the hypomethylated profile was more frequent in the group of patients who had recovered from mucositis. It was concluded that the methylation profiles of CAT, SOD3, and IL6 are common profiles for oral cells of children and adolescents and have no association with oral mucositis or exposure to chemotherapy with MTX®. Hypomethylation of TNF-α is associated with oral mucosal recovery in oncopediatric patients who developed oral mucositis during chemotherapy.

Genetic polymorphisms and clinical parameters associated with renal toxicity in Thai hematologic malignancy patients receiving high dose methotrexate.

High-dose methotrexate (HD-MTX) is a widely used chemotherapy regimen for hematologic malignancies such as lymphomas and acute lymphoblastic leukemia, but its use can lead to adverse effects, including acute kidney injury (AKI), impaired liver function, and mucositis, causing extended hospital stays and delayed subsequent chemotherapy. Our study aimed to investigate the predictive factors for renal toxicities associated with HD-MTX in Thai patients undergoing treatment for hematologic malignancies. We enrolled 80 patients who underwent MTX-containing regimens, analyzing 132 chemotherapy cycles. The most common disease was primary central nervous system lymphoma (33%). Genetic polymorphisms were examined using the MassARRAY® system, identifying 42 polymorphisms in 25 genes. Serum creatinine and MTX levels were measured 24 and 48 h after MTX administration. For the primary outcome, we found that the allele A of MTRR rs1801394 was significantly related to renal toxicity (odds ratio 2.084 (1.001-4.301), p-value 0.047). Patients who exceeded the MTX threshold levels at 24 h after the dose had a significantly higher risk of renal toxicity (OR (95%CI) = 6.818 (2.350-19.782), p < 0.001). Multivariate logistic regression analysis with a generalized estimated equation revealed hypertension and age as independent predictors of increased MTX levels at 24 h after the given dose.

Skeletal muscle mass during chemotherapy for haematological malignancies: a retrospective study.

OBJECTIVE: This study investigated whether baseline or alteration in muscle mass affects complications during chemotherapy or overall survival (OS) in haematological malignancies. METHODS: Skeletal Muscle Index (SMI) was evaluated by bioimpedance analysis before and after chemotherapy in patients with haematological malignancies, and the association between muscle mass and clinical data was retrospectively analysed. RESULTS: Exactly 104 patients were enrolled, with a mean age of 62.2 years. SMI was 7.85 and 6.08 in male and female patients under 65 years and 7.10 and 5.92 over 65 years, before chemotherapy, respectively. Lower baseline SMI was not correlated with worse OS in total patients (p=0.915). After a median measurement interval of 30 days after chemotherapy (n=67), body weight and SMI decreased by 2.73% and 2.87% (mean), respectively. The decrease in body weight correlated with the loss of trunk muscle mass (R2=0.2107) but was more strongly associated with the loss of lower limbs muscle mass (R2=0.3985). The muscle mass of lower limbs significantly decreased in lymphoma patients who experienced febrile neutropenia (-0.42% vs -6.04%, p=0.040). OS significantly decreased in lymphoma patients with loss of lower limbs muscle ≥2.8% (p=0.0327). CONCLUSIONS: Muscle loss occurred following anticancer treatments, significantly contributing to worse outcomes. Body composition assessment and relevant multimodal prevention of muscle loss may be vital for patients receiving chemotherapy for haematological malignancies.

[Therapy of mental disorders in patients with hematological malignancies]. / Terapiya nepsikhoticheskikh psikhicheskikh rasstroistv u bol'nykh s zabolevaniyami sistemy krovi.

OBJECTIVE: To assess the possibilities of therapy with minimal effective doses (MED) of psychotropic drugs for mental disorders (MD) that manifest during the treatment of hematological malignancies (HM). MATERIAL AND METHODS: A prospective study was conducted at the National Medical Research Center for Hematology of the Russian Ministry of Health (Moscow), which included 204 (39.4%) men and 314 (60.6%) women (518 patients in total), aged 17 to 83 years (median 45 years), with various HM, in which the manifestation of MD occurred during the treatment of the underlying disease. To minimize the side-effects of psychotropic drugs and given the relatively mild level of MD, psychopharmacotherapy of patients was carried out mainly at MED. The severity of MD, manifested in patients, was assessed by the illness severity scale of the Clinical Global Impression (CGI) scale, and the effectiveness of the treatment was assessed by the improvement scale (CGI-I). RESULTS: Mainly mild (188, 36%) and moderately pronounced (270, 52%) MD were noted in patients with HM during the treatment of the underlying disease. Severe psychopathological disorders (60, 12%) were observed much less often. Because of psychopharmacotherapy with MED, patients experienced a very significant (97, 19%) and significant improvement (354, 68%) of their mental state, less often the improvement was regarded as minimal (67, 13%). Therefore, almost all patients showed a stable relief of MD; in 87% (95% CI 84-90) of patients, this improvement was significant. CONCLUSION: The tactics of treatment MD that manifest in patients with HM with MED of psychotropic drugs turned out to be therapeutically effective according to the results of the assessment on CGI scales.

Metronomic chemotherapy in hematology: Lessons from preclinical and clinical studies to build a solid rationale for future schedules.

Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting multiple targets and reducing toxicity of antineoplastic drugs. This minireview will summarize preclinical and clinical studies on cytotoxic drugs given at weekly, daily, or at continuous metronomic schedules alone or in combination with novel targeted agents for hematological malignancies, including lymphoma, multiple myeloma, and leukemia. Most of the preclinical in vitro and in vivo studies have reported a significant benefit of both mCHEMO monotherapy and combinatorial regimens compared with chemotherapy at the maximum tolerated dose. However, the combination of mCHEMO with targeted drugs is still little explored in the hematologic clinical setting. Data obtained from preclinical studies on low dose metronomic chemotherapy in hematological malignancies clearly suggested the possibility to clinically investigate more tolerable and effective strategies for the treatment of patients with advanced hematological malignancies, or at least for those frail and elderly patients, who are not eligible or resistant to standard treatments.

Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers.

TP53-mutant blood cancers remain a clinical challenge. BH3-mimetic drugs inhibit BCL-2 pro-survival proteins, inducing cancer cell apoptosis. Despite acting downstream of p53, functional p53 is required for maximal cancer cell killing by BH3-mimetics through an unknown mechanism. Here, we report p53 is activated following BH3-mimetic induced mitochondrial outer membrane permeabilization, leading to BH3-only protein induction and thereby potentiating the pro-apoptotic signal. TP53-deficient lymphomas lack this feedforward loop, providing opportunities for survival and disease relapse after BH3-mimetic treatment. The therapeutic barrier imposed by defects in TP53 can be overcome by direct activation of the cGAS/STING pathway, which promotes apoptosis of blood cancer cells through p53-independent BH3-only protein upregulation. Combining clinically relevant STING agonists with BH3-mimetic drugs efficiently kills TRP53/TP53-mutant mouse B lymphoma, human NK/T lymphoma, and acute myeloid leukemia cells. This represents a promising therapy regime that can be fast-tracked to tackle TP53-mutant blood cancers in the clinic.

Hepatitis B relapse after entecavir or tenofovir alafenamide cessation under anti-viral prophylaxis for cancer chemotherapy.

BACKGROUND: No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). METHODS: A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. RESULTS: The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment. CONCLUSIONS: In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.

Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies.

Molecular targeted drugs and chimeric antigen receptor (CAR) T cell therapy represent specific biological treatments that have significantly improved the efficacy of treating hematologic malignancies. However, they face challenges such as drug resistance and recurrence after treatment. Combining molecular targeted drugs and CAR-T cells could regulate immunity, improve tumor microenvironment (TME), promote cell apoptosis, and enhance sensitivity to tumor cell killing. This approach might provide a dual coordinated attack on cancer cells, effectively eliminating minimal residual disease and overcoming therapy resistance. Moreover, molecular targeted drugs can directly or indirectly enhance the anti-tumor effect of CAR-T cells by inducing tumor target antigen expression, reversing CAR-T cell exhaustion, and reducing CAR-T cell associated toxic side effects. Therefore, combining molecular targeted drugs with CAR-T cells is a promising and novel tactic for treating hematologic malignancies. In this review article, we focus on analyzing the mechanism of therapy resistance and its reversal of CAR-T cell therapy resistance, as well as the synergistic mechanism, safety, and future challenges in CAR-T cell therapy in combination with molecular targeted drugs. We aim to explore the benefits of this combination therapy for patients with hematologic malignancies and provide a rationale for subsequent clinical studies.

[Research Progress on the Role of Berberine in Hematologic Malignancies and Its Related Mechanisms --Review].

Berberine, a traditional Chinese medicine, is an isoquinoline alkaloid extracted from the rhizome of Coptis chinensis. It has anti-inflammatory and antidiarrheal effects and is commonly used in the treatment of infections and gastrointestinal diseases. In recent years, studies have found that berberine can play a wide range of anti-cancer effects in the treatment of leukemia, lymphoma, multiple myeloma, etc. In hematologic malignancies, berberine can induce autophagy, promote apoptosis, regulate cell cycle, inhibit inflammatory response, cause oxidative damage to cancer cells and interact with miRNA to inhibit the proliferation, migration and colony formation of cancer cells. This paper will review the role and related mechanisms of berberine in hematological malignancies.

Targeting PRL phosphatases in hematological malignancies.

INTRODUCTION: Phosphatase of regenerating liver (PRL) family proteins, also known as protein tyrosine phosphatase 4A (PTP4A), have been implicated in many types of cancers. The PRL family of phosphatases consists of three members, PRL1, PRL2, and PRL3. PRLs have been shown to harbor oncogenic potentials and are highly expressed in a variety of cancers. Given their roles in cancer progression and metastasis, PRLs are potential targets for anticancer therapies. However, additional studies are needed to be performed to fully understand the roles of PRLs in blood cancers. AREAS COVERED: In this review, we will summarize recent studies of PRLs in normal and malignant hematopoiesis, the role of PRLs in regulating various signaling pathways, and the therapeutic potentials of targeting PRLs in hematological malignancies. We will also discuss how to improve current PRL inhibitors for cancer treatment. EXPERT OPINION: Although PRL inhibitors show promising therapeutic effects in preclinical studies of different types of cancers, moving PRL inhibitors from bench to bedside is still challenging. More potent and selective PRL inhibitors are needed to target PRLs in hematological malignancies and improve treatment outcomes.