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Optical genome mapping (OGM) is a novel non-sequencing genetic analysis technology that enables high-precision analysis of structural variations across the entire genome. It possesses unique technical advantages, and its procedural simplicity makes it easy to implement. In recent years, the application efficacy of OGM technology in the analysis of genomic structural variations in hematologic malignancies has been widely validated and recognized. Increasing evidence indicates that the application of OGM technology can help improve the genetic diagnosis, prognostic stratification and treatment guidance of hematologic malignancies. This article draws upon pertinent reports from the 65th American Society of Hematology Annual Meeting to provide an overview of the progress in applying OGM technology for the precise diagnosis and treatment of hematologic malignancies.
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Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic protein that plays a key role in promoting cell survival in multiple myeloma, acute myeloid leukemia and non-Hodgkin lymphoma. MCL-1 is highly expressed in a variety of hematological malignancies, which is one of the important factors leading to poor prognosis and chemoresistance in patients with hematological malignancies. Therefore, MCL-1 is an important therapeutic target for hematological malignancies. Several MCL-1 inhibitors have entered clinical trials, including S63845, AZD5991, S64315, AMG-176, and AMG-397. The treatment plans used for hematological malignancies include monotherapy with MCL-1 inhibitors, as well as combination therapy with B cell lymphoma 2 inhibitors or immunomodulatory drugs, all indicating that MCL-1 inhibitors may be a breakthrough point for targeted treatment of hematological malignancies.
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Abstract Background An increased risk of Secondary Malignancies (SMs) in Mycosis Fungoides (MF) has been suggested previously. However, the relationship between this risk and the features of MF is not well-known. Objective To investigate the rate and types of SMs in a large cohort of MF patients focusing on the associated features of these patients. Methods The demographic features, subtype, and stage of MF, as well as the temporal relationship between the diagnosis of MF and the development of SMs were determined. Major clinical features of MF in this group were compared with MF patients without association of SMs. Results Among 730 MF patients with a mean follow-up period of 67.9 ± 52.4 months, 56 SMs were identified in a total of 52 (7.1%) patients. While 28.8% of patients were previously diagnosed with other malignancies, then subsequently had a diagnosis of MF, it was vice versa in 53.8% of patients. Most of the SM-associated MF patients had early-stage (80.7%) and classical type of MF (86.5%) without a significant difference from MF patients without association of SMs; 85.5% and 72.5%, respectively. The most commonly identified SMs were hematologic malignancies (64.3%) including lymphomatoid papulosis (n = 22), Hodgkin's lymphoma (n = 4), non-Hodgkin's lymphoma (n = 5), polycythemia vera (n = 2). Other most commonly associated malignancies were breast cancer (n = 4), prostate cancer (n = 3), renal cell carcinoma (n = 2), melanoma (n = 2), and Kaposi's sarcoma (n = 2). Study limitations A single tertiary dermatology center study with a retrospective design. Conclusion Apart from the well-known lymphomatoid papulosis association, systemic hematological malignancies were also quite common in the large cohort of MF patients.
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Abstract When a SARS-CoV-2 RT-qPCR test is performed, it may determine an indirect measureof viral load called cycle threshold (Ct). Respiratory samples with Ct <25.0 cycles are consideredto contain a high viral load. We aimed to determine whether SARS-CoV-2 Ct at diagnosis couldpredict mortality in patients with hematologic malignancies (lymphomas, leukemias, multiplemyeloma) who contracted COVID-19. We included 35 adults with COVID-19 confirmed by RT-qPCR performed at diagnosis. We evaluated mortality due to COVID-19 rather than mortalitydue to the hematologic neoplasm or all-cause mortality. Twenty-seven (27) patients survivedand 8 died. The global mean Ct was 22.8 cycles with a median of 21.7. Among the survivors,the mean Ct was 24.2, and the median Ct value was 22.9 cycles. In the deceased patients, themean Ct was 18.0 and the median Ct value was 17.0 cycles. Using the Wilcoxon Rank Sum test,we found a significant difference (p = 0.035). SARS-CoV-2 Ct measured in nasal swabs obtainedat diagnosis from patients with hematologic malignancies may be used to predict mortality.
Resumen Cuando se realiza una RT-qPCR para SARS-CoV-2, es posible determinar una medidaindirecta de la carga viral llamada umbral de ciclado (Ct). Las muestras respiratorias con Ct<25,0 ciclos se consideran de alta carga viral. Nos propusimos determinar si el Ct para SARS-CoV-2 al diagnóstico predice la mortalidad en pacientes con neoplasias hematológicas (linfomas,leucemias, mielomas) que contrajeron COVID-19. Incluimos 35 adultos con COVID-19 confirmadopor RT-qPCR al diagnóstico. Evaluamos la mortalidad por COVID-19, no la mortalidad por la neo-plasia hematológica o la mortalidad por cualquier causa. De los 35 pacientes, 27 sobrevivierony 8 fallecieron. El Ct global medio fue 22,8 ciclos con una mediana de 21,7 ciclos. Entre lossobrevivientes, el Ct medio fue 24,2 ciclos con una mediana de 22,9 ciclos. Entre los fallecidos,el Ct medio fue 18,0 y el Ct mediano fue 17,0 ciclos. Empleando la prueba de suma de rangosde Wilcoxon, encontramos una diferencia significative (p = 0,035). En pacientes con neoplasiashematológicas infectados con coronavirus, el Ct de SARS-CoV-2 medido en hisopados nasales almomento del diagnóstico podría ser utilizado para predecir la mortalidad.
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Los pacientes con malignidades hematológicas tienen un riesgo más alto de hospitalización, admisión a cuidado crítico y muerte cuando contraen COVID-19. En este grupo se ha propuesto la vacunación y los refuerzos para disminuir el riesgo de complicaciones. Sin embargo, es posible ver una pobre respuesta humoral y celular a las vacunas. En esta revisión se presenta la evidencia sobre la respuesta a la vacunación, poniendo de presente algunas patologías y tratamientos que pueden disminuirla de forma significativa. Los pacientes con neoplasias hematológicas se deben considerar en riesgo de complicaciones, incluso después de haber sido vacunados de forma completa y haber recibido los refuerzos. Se debe mantener la vigilancia de forma estrecha después de haber sido vacunados y evaluar la posibilidad de otras estrategias (medicamentos, anticuerpos monoclonales) para la prevención o el manejo de COVID-19.
Patients with hematological malignancies have a higher risk of hospital admission, critical care and death when they suffer from COVID-19. In this group of patients, vaccination and boosters have been proposed to mitigate the risk of complications. However, it is possible to observe a diminished rate of humoral and cellular response. In this review, evidence is shown about the response to COVID-19 vaccination, considering some specific pathologies and treatments that can affect such response in a significant account. Patients with malignant neoplasm must be considered at risk of COVID-19 complications, even after a complete vaccine schedule and boosters. Surveillance must be maintained after vaccination over these patients and other strategies must be considered (drugs, monoclonal antibodies) for prevention and management of COVID-19.
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Humans , Hematologic Neoplasms/immunology , COVID-19/prevention & control , Risk Factors , Immunosuppression Therapy , Immunocompromised Host , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , COVID-19/complications , Antineoplastic Agents/adverse effectsABSTRACT
The anti-apoptotic protein bcl-2, a key regulator of the intrinsic apoptotic pathway, is frequently overexpressed in cells of hematologic malignancies, and the small molecule inhibitor venetoclax that targets this apoptotic pathway has shown promising efficacy in the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma. The survival and prognosis of patients with acute myeloid leukemia who are of advanced age or who are unsuitable for strong induction chemotherapy because of comorbidities also have significantly improved, but some patients develop progressive drug resistance during the course of venetoclax treatment, which affects the efficacy of medical therapy. This article reviews the action mechanism, therapeutic progress and resistance mechanism of venetoclax in hematologic malignancies.
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The incidence of hematologic malignancies is increasing, and although new drugs and treatments have made great progress, relapse and drug resistance are still urgent problems to be solved. Exosomes are tiny membrane vesicles secreted in cells that carry lipid bilayer membrane structures including mRNA, microRNA and proteins. It carries and transmits important signaling molecules, forming an entirely new intercellular information transfer system that exhibits a wide range of biological properties and functions in organisms. Tumor cell exosomes are confirmed to contribute to cancer cell proliferation, angiogenesis, invasiveness, distant metastasis and drug resistance. Multiple studies have shown that exosomes from some malignant hematological tumor cells are closely related to tumor resistance. This review summarizes the research progress of exosomes in the mechanism of drug resistance of hematologic malignancies, in order to provide a theoretical basis for the clinical treatment of hematologic malignancies.
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The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase, which is widely studied in histone methylation modification. It can promote epigenetic gene silencing and mediate the occurrence of tumors through a variety of regulatory mechanisms. The gain-of-function and loss-of-function mutations of EZH2 have been confirmed in many cancers. At present, with the extensive attention paid to the regulatory role of EZH2 in epigenetic mechanism, the exact way in which EZH2 imbalance affects the pathogenesis of hematologic malignancies remains to be clarified. This article reviews the pathogenetic role of EZH2 in hematological tumors, and hope to find new targets for the prevention and treatment of hematological tumors.
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Chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved good efficacy in treatment of hematological malignancies. As a precise and individualized treatment method, CAR-T is gradually moving towards commercialization. In addition to the introduction of corresponding policies and guiding principles, the related detection protocols should also be updated and improved to maximize its effect and achieve precise individualization. This article introduces and expands the concept of "companion diagnostics" that first appeared in targeted drugs, and introduces the significances of various detection technologies and biomarkers for patient screening, safety monitoring and evaluation of efficacy and CAR-T function in the whole process of CAR-T treatment.
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CD99 gene encodes a transmembrane protein and participates in cell differentiation, adhesion, migration and protein transport. The expression of CD99 is generally low in most normal tissues and cells, and CD99 is differentially expressed in bone marrow and the surface of lymphatic hematopoietic cells. This article reviews the research progress of CD99 in hematological diseases, explores the role of CD99 in myeloid and lymphocytic leukemia, and the significance of CD99 as a therapeutic target for hematological malignancies.
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Objective:To evaluate the diagnostic value and safety of transbronchial lung biopsy and bronchoalveolar lavage (BAL) in pulmonary complications in patients with hematological tumors.Methods:A retrospective analysis was performed on 68 patients with hematological tumors combined with lung lesions from The University of Hong Kong-Shenzhen Hospital and The Third People's Hospital of Shenzhen from May 2016 to May 2022, including 37 males, 31 females, with a median age of 56 years (age range 21-90 years), among which 20 patients were >65 years old. Diagnostic fiberoptic bronchoscopy was performed with signs including fever, cough, hypoxemia, hemoptysis, unexplained dyspnea, and imaging changes. Patients with pulmonary masses were evaluated for transbronchial lung biopsy, including inner and outer leaf mass and high-density shadow of lung leaves, pathological and special staining of biopsy tissue (Grocott staining), BAL acquisition of bronchoalveolar lavage fluid (BALF) for microbiological smear/culture, cytomegalovirus, Pneumocystis jirovecii and Mycobacterium tuberculosis (TB) smear, TB DNA, TB and fungal culture. Etiological analysis of pulmonary complications and observation of the complications associated with fiberoptic bronchoscopy in patients with hematological tumors were conducted. Results:BALF test was performed in all patients after bronchoscopy, bronchoscopic lung tissue biopsy was performed in 46 cases. The total number of confirmed pathogenic infections was 40, including 12 cases of fungal infections, 9 cases of bacterial infections (2 cases each of E. faecalis and Pseudomonas aeruginosa, 1 case of Staphylococcus aureus, 1 case of Klebsiella pneumoniae, 1 case of E. coli, 1 case of coagulase-negative Staphylococcus, and 1 case of Streptococcus mitis), 9 cases of viral infection (5 cases of cytomegalovirus, 3 cases of parainfluenza virus type Ⅲ, and 1 case of respiratory syncytial virus), 4 confirmed cases of Pneumocystis jirovecii pneumonia, 3 cases of suspected mixed infection of Pneumocystis jirovecii and fungi, 1 case of Cryptococcus, 2 cases of suspected TB infection. No pathogenic organisms were found in 28 cases, including 6 cases of mechanized pneumonia, 6 cases associated with a history of hematological tumors, and 16 cases of other unidentified pathogens. All patients did not experience death or other serious complications caused by bronchoscopy complications. Conclusion:Pulmonary complications are common in patients with hematological tumors, and the application of transbronchial lung biopsy has good safety. Early examination of fiberoptic bronchoscopy can provide pathogenic diagnostic evidence of bacterial, fungal, Pneumocystis jirovecii and viral infections, thus improving the diagnostic rate.
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Hematological malignancies are suitable diseases for radioimmunotherapy because of their high sensitivity to radiation and well-defined immunophenotypes. Beta emitters like 131I and 90Y have achieved some outcomes in radioimmunotherapy of hematological malignancies. Compared with beta particles, alpha particles have higher linear energy transfer, greater relative biological effects and shorter range, which give alpha particles the ability to kill tumor cells more effectively with less damage to normal tissue. This review summarizes the current studies of targeted alpha-particle therapy in hematological malignancies.
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As medical research progresses, an increasing number of genetic variations are being incorporated into international guidelines for the diagnosis and treatment of hematological malignancies. In several international guidelines updated in 2022, more emphasis is placed on the importance of genetic variation in the classification and prognosis assessment of hematological malignancies. The clinical diagnosis and treatment of hematological malignancies have entered the era of precision medicine and genomics, relying increasingly on the application of high-throughput sequencing technology.
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The relationship between pyroptosis and immune microenvironment and disease has received increasing attention. Pyroptosis plays a dual role in anti-tumor immunotherapy by promoting the release of inflammatory factors, forming the tumor microenvironment and suppressing tumour immunity on the one hand, and inducing the tumour inflammatory response to inhibit the proliferation of tumor cells on the other hand. The relationship between pyroptosis, immune microenvironment and tumors is different in different tissues and genetic backgrounds. This article reviews the molecular mechanisms of pyroptosis and the regulatory role of tumor immune microenvironment in hematologic malignancies, with a view to providing ideas for the anti-hematologic malignancies treatment and research based on the target of pyroptosis-regulated immune microenvironment.
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ABSTRACT Objectives: to identify the elements for assistance to patients with hematological malignancies to propose a care line. Methods: this is a scoping review, anchored in the JBI theoretical framework, with searches carried out in April 2021, in eight electronic databases and 10 repositories of theses and dissertations. Results: the final sample consisted of 93 studies, and the main forms of assistance provided that can support a care line for this public were imaging tests, immunophenotyping, chemotherapy regimens, radiotherapy, infection management, assessment of nutritional status, maintenance of oral function, symptom management and screening for second malignancies. Conclusions: the elaboration of a care line for onco-hematologic patients is necessary, considering the complexity surrounding the diagnosis and treatment of hematologic malignancies, in addition to the difficulties that are imposed in relation to access and continuity of care in the network.
RESUMEN Objetivos: identificar los elementos para la asistencia a pacientes con neoplasias hematológicas para proponer una línea de atención. Métodos: se trata de una revisión de alcance, anclada en el marco teórico del JBI, con búsquedas realizadas en abril de 2021 en ocho bases de datos electrónicas y 10 repositorios de tesis y disertaciones. Resultados: la muestra final estuvo compuesta por 93 estudios, y las principales formas de asistencia brindadas que pueden sustentar una línea de atención a este público fueron pruebas de imagen, inmunofenotipificación, regímenes de quimioterapia, radioterapia, manejo de infecciones, evaluación del estado nutricional, mantenimiento de la función oral, manejo de síntomas y detección de segundas neoplasias malignas. Conclusiones: es necesario el desarrollo de una línea de atención al paciente oncohematológico, dada la complejidad que rodea al diagnóstico y tratamiento de las neoplasias hematológicas, además de las dificultades que se imponen en relación al acceso y continuidad de la atención en una red.
RESUMO Objetivos: identificar os elementos para assistência a pacientes com neoplasias hematológicas para propor uma linha de cuidado. Métodos: trata-se de uma scoping review, ancorada no referencial teórico do JBI, com buscas realizadas em abril de 2021 em oito bases de dados eletrônicas e 10 repositórios de teses e dissertações. Resultados: a amostra final foi composta por 93 estudos, e as principais formas de assistências prestadas que podem embasar uma linha de cuidado para esse público foram exames de imagem, imunofenotipagem, regimes quimioterápicos, radioterapia, gestão de infecções, avaliação do estado nutricional, manutenção da função oral, gerenciamento de sintomas e rastreio para segundas neoplasias. Conclusões: a elaboração de uma linha de cuidados para pacientes onco-hematológicos se faz necessária, tendo em vista a complexidade que cerca o diagnóstico e tratamento das neoplasias hematológicas, além das dificuldades que se impõem em relação ao acesso e continuidade do cuidado em rede.
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RESUMEN El linfoma del tejido linfoide asociado a las mucosas es una variedad poco común y recientemente descubierta del linfoma no Hodgkin. Suele presentarse en la sexta década de la vida, con un predominio del sexo femenino y en sitios como el tracto digestivo, pulmón, riñón, hígado, piel, y solo en el 2 % de los casos, en la glándula tiroides, donde en muchas ocasiones se asocia a la tiroiditis autoinmune de Hashimoto. Su evolución es favorable cuando se diagnostica en estadios iniciales de la enfermedad. Se presenta una paciente de 22 años, con una historia de trastornos endocrinos, perceptibles desde la adolescencia, a quien se le diagnosticó una tiroiditis de Hashimoto, sobre la que subyacía un linfoma del tejido linfoide asociado a las mucosas, y que evolucionó satisfactoriamente luego del tratamiento quirúrgico.
ABSTRACT Mucosa-associated lymphoid tissue lymphoma is a rare and recently discovered variant of non-Hodgkin's lymphoma. It usually occurs in the sixth decade of life, with a predominance of females and may be observed in sites such as the digestive tract, lung, kidney, liver, skin, and only in 2% of cases, in the thyroid gland, where in many occasions it is associated with Hashimoto's autoimmune thyroiditis. Its evolution is favorable when it is diagnosed in the initial stages of the disease. We present a 22-year-old female patient with a history of perceptible endocrine disorders since adolescence, who was diagnosed with Hashimoto's thyroiditis, underlying mucosa-associated lymphoid tissue lymphoma, and who evolved satisfactorily after surgical treatment.
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Lymphoma, Non-Hodgkin , Hematologic Neoplasms , Hashimoto DiseaseABSTRACT
BACKGROUND: COVID-19 infection can be especially severe in certain risk populations such as patients with hematologic malignancies. Aim: To describe the characteristics and clinical outcomes of a population of patients with hematologic malignancies and COVID-19. MATERIAL AND METHODS: Review of medical records of patients with COVID-19 and hematologic malignancies, treated in Hematology Service of a regional hospital in Chile, between April 1 and October 30, 2020. Demographic characteristics, chronic comorbidities and clinical characteristics related to the underlying disease and COVID-19 infection were recorded. Results: Thirty adults aged 17 to 73 years (67% men) with COVID-19 confirmed by RT-PCR, were evaluated. Forty percent had comorbidities, mainly hypertension (30%), obesity (27%) and diabetes (10%). Two thirds of cases came from a nosocomial outbreak and 77% were symptomatic. Half of the cases had mild disease and 20% required mechanical ventilation. Five patients (17%) died from COVID 19. Female sex, the presence of comorbidities and obesity were more common among deceased patients. Only 1 of 5 deceased patients were in complete remission. No differences were found in the mean survival according to requirement for intubation or the presence of complete remission. CONCLUSIONS: This population with hematologic malignancies and COVID-19 had special characteristics leading to a greater fatality rate which, in this series, does not increase with the use of mechanical ventilation.
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Humans , Male , Female , Adult , Hematologic Neoplasms/complications , COVID-19/epidemiology , Hypertension , SARS-CoV-2 , Obesity/complications , Obesity/epidemiologyABSTRACT
INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.
BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.
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Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Hypoalbuminemia/drug therapy , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Neoplasms/complications , Neoplasms/drug therapy , Neutropenia/drug therapy , beta-Lactamases , Carbapenems/therapeutic use , Carbapenems/pharmacology , Retrospective Studies , Enterobacteriaceae , Klebsiella pneumoniae , Anti-Bacterial Agents/therapeutic useABSTRACT
Lymphoma-associated hemophagocytic syndrome (LAHS) accounts for a large proportion of secondary hemophagocytic syndrome (HPS) and has a poor prognosis. LAHS can be divided into two categories: HPS combined with chemotherapy and lymphoma-induced HPS. The key to the treatment of HPS combined with chemotherapy is to control the infection. While the treatment of lymphoma-induced HPS is complicated, there are new strategies in addition to traditional methods. Timely and appropriate treatment can significantly improve the short-term and long-term prognosis of patients. This article summarizes the progress in treatment of LAHS.
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With the increasing incidence of hematologic malignancies, exploring its pathogenesis and new treatment strategies has become new research directions. The development of high-throughput sequencing technology has led to the recognition of long non-coding RNA, which plays an important role in the development of life and the regulation of diseases. As the first reported long non-coding RNA, H19 acts as an oncogene to take part in various pathological processes in the growth and metastasis of tumors. However, the multiple roles of H19 in hematologic malignancies are lack of systematic summary. This article reviews the role of H19 in carcinogenesis, progression and drug resistance mechanism of hematologic malignancies, in order to provide guidance for further research.