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BMC Genomics 2022 Jun 24;23(1):467. Epub 2022 Jun 24.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: T cell acute lymphoblastic leukemia (T-ALL) defines a group of hematological malignancies with heterogeneous aggressiveness and highly variable outcome, making therapeutic decisions a challenging task. We tried to discover new predictive model for T-ALL before treatment by using a specific pipeline designed to discover aberrantly active gene.

Results: The expression of 18 genes was significantly associated with shorter survival, including ACTRT2, GOT1L1, SPATA45, TOPAZ1 and ZPBP (5-GEC), which were used as a basis to design a prognostic classifier for T-ALL patients. Read More

Blood Cancer J 2022 Jun 24;12(6):96. Epub 2022 Jun 24.

Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, P. R. China.

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. Read More

Leuk Lymphoma 2022 Jun 24:1-11. Epub 2022 Jun 24.

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, P.R. China.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of ALL. We retrospectively studied 70 cases with Ph-like ALL and here present the largest study of CAR-T cell treatment and haplo-HSCT for this leukemia. Median age was 26 years and median leukocyte count was 31. Read More

Front Oncol 2022 7;12:911567. Epub 2022 Jun 7.

Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.

It is urgently necessary to reduce the adverse effects of chemotherapy while maintaining their cure high rates for children with acute lymphoblastic leukemia (ALL). The present study aimed to determine whether the dose intensity of daunorubicin during the remission-induction phase could be reduced for low-risk patients with ALL. A total of 2396 eligible patients, who participated in CCCG-ALL-2015 study and were provisionally assigned to the low-risk group, were included and divided into single-dose group and double-dose group according to the dosage of daunorubicin during the remission-induction phase. Read More

Indian J Hematol Blood Transfus 2022 Jul 28;38(3):499-507. Epub 2021 Sep 28.

Department of Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, India.

Leukocyte cell population data (CPD) generated by hematology auto analyzers are reported to be useful in screening of sepsis patients. However, there is a paucity of literature highlighting the utility of CPD in screening of acute leukemias (AL). Leucocyte CPD obtained by Sysmex XN1000 hematology analyzer from 210 cases of ALs [22 acute promyelocytic leukemia (APL), 79 non-APL acute myeloid leukemia (non-APL-AML) and 109 acute lymphoblastic leukemia (ALL)] were compared with 100 healthy and 52 reactive controls. Read More

Pharmaceuticals (Basel) 2022 Jun 14;15(6). Epub 2022 Jun 14.

Health Sciences School, University of Brasilia, Brasilia 70910-900, Brazil.

L-asparaginase is an important enzyme in the pharmaceutical field used as treatment for acute lymphoblastic leukemia due to its ability to hydrolyze L-asparagine, an essential amino acid synthesized by normal cells, but not by neoplastic cells. Adverse effects of L-asparaginase formulations are associated with its glutaminase activity and bacterial origin; therefore, it is important to find new sources of L-asparaginase produced by eukaryotic microorganisms with low glutaminase activity. This work aimed to identify the L-asparaginase gene sequence from , a filamentous fungus isolated from the Brazilian Savanna (Cerrado) soil with low glutaminase activity, and to biosynthesize higher yields of this enzyme in the yeast . Read More

Medicina (Kaunas) 2022 May 29;58(6). Epub 2022 May 29.

Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Japan.

Recent advances in chemotherapy have led to the emergence of new types of anticancer agents. With these advances, cases of side effects that have not been witnessed in the past have emerged. The systems of side effect evaluation and their grading have been based on the existing knowledge, such as the CTCAE (Common Terminology Standard for Adverse Events) for evaluating adverse drug reactions in cancer chemotherapy clinical trials. Read More

J Pers Med 2022 May 25;12(6). Epub 2022 May 25.

Oncology Research Nucleus, Universidade Federal do Pará, Belém 66073-005, PA, Brazil.

A number of genomic variants related to native American ancestry may be associated with an increased risk of developing Acute Lymphoblastic Leukemia (ALL), which means that Latin American and hispanic populations from the New World may be relatively susceptible to this disease. However, there has not yet been any comprehensive investigation of the variants associated with susceptibility to ALL in traditional Amerindian populations from Brazilian Amazonia. We investigated the exomes of the 18 principal genes associated with susceptibility to ALL in samples of 64 Amerindians from this region, including cancer-free individuals and patients with ALL. Read More

Diagnostics (Basel) 2022 Jun 4;12(6). Epub 2022 Jun 4.

Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden.

Monoclonal rearrangements of immunoglobulin (Ig) genes and T-cell receptor (TCR) genes are used for minimal measurable disease in acute lymphoblastic leukemia (ALL). The golden standard for screening of gene rearrangements in ALL has been PCR GeneScan and Sanger sequencing, which are laborsome and time-consuming methods. More rapid next-generation sequencing methods, such as LymphoTrack could possibly replace PCR GeneScan and Sanger sequencing for clonality assessment. Read More

Cells 2022 Jun 13;11(12). Epub 2022 Jun 13.

Institute of Biological Chemistry, Biophysics & Engineering (IB3), School of Engineering &Physical Sciences, Heriot Watt University, Edinburgh EH14 4AS, UK.

Phosphoribosyl pyrophosphate synthetase (PRS EC 2.7.6. Read More

Biomolecules 2022 Jun 9;12(6). Epub 2022 Jun 9.

Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.

Despite the excellent prognosis for children and adolescents with acute lymphoblastic lymphoma (ALL), the involvement of the central nervous system (CNS) represents a major therapeutic challenge. Patients who develop CNS relapse have a very poor prognosis, and since current methods cannot reliably identify patients with CNS involvement or patients at high risk of CNS relapse, all children with ALL receive CNS-directed treatment. The current golden standard for detecting CNS involvement is the assessment of cytomorphology on cytospin slides of cerebrospinal fluid (CSF). Read More

Cancers (Basel) 2022 Jun 16;14(12). Epub 2022 Jun 16.

Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.

Despite the development of metabolism-based therapy for a variety of malignancies, resistance to single-agent treatment is common due to the metabolic plasticity of cancer cells. Improved understanding of how malignant cells rewire metabolic pathways can guide the rational selection of combination therapy to circumvent drug resistance. Here, we show that human T-ALL cells shift their metabolism from oxidative decarboxylation to reductive carboxylation when the TCA cycle is disrupted. Read More

Cancers (Basel) 2022 Jun 11;14(12). Epub 2022 Jun 11.

Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. Read More

Biomedicines 2022 May 24;10(6). Epub 2022 May 24.

Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.

Small nucleolar RNAs (snoRNAs) are responsible for post-transcriptional modification of ribosomal RNAs, transfer RNAs and small nuclear RNAs, and thereby have important regulatory functions in mRNA splicing and protein translation. Several studies have shown that snoRNAs are dysregulated in human cancer and may play a role in cancer initiation and progression. In this review, we focus on the role of snoRNAs in normal and malignant B-cell development. Read More

Sci Rep 2022 Jun 23;12(1):10670. Epub 2022 Jun 23.

Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Despite recent progress in acute lymphoblastic leukemia (ALL) therapies, a significant subset of adult and pediatric ALL patients has a dismal prognosis. Better understanding of leukemogenesis and recognition of germline genetic changes may provide new tools for treating patients. Given that hematopoietic stem cell transplantation, often from a family member, is a major form of treatment in ALL, acknowledging the possibility of hereditary predisposition is of special importance. Read More

In Vivo 2022 Jul-Aug;36(4):1637-1642

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.;

Background/aim: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. Read More

Leuk Res 2022 Jun 8;119:106885. Epub 2022 Jun 8.

Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, CA, USA. Electronic address:

Background: Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated. Read More

Blood Adv 2022 Jun 23. Epub 2022 Jun 23.

Kyoto University, Kyoto, Japan.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising treatment for adult acute lymphoblastic leukemia (ALL), an intractable hematological malignancy. The trends in allo-HCT outcomes over the past 30 years were examined to verify the efficacy of evolving treatment methods and to identify further challenges. We analyzed data from a registry database that included 8467 adult ALL patients who underwent their first allo-HCT between 1990 and 2019. Read More

Int J Hematol 2022 Jun 23. Epub 2022 Jun 23.

Beijing Lu Daopei Institute of Hematology, Beijing, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for B-cell acute lymphoblastic leukemia (B-ALL). Although allo-HSCT can be curative for some B-ALL patients, relapse still occurs in some patients following allo-HSCT. Conventional chemotherapies show poor efficacy in B-ALL patients who have relapsed following allo-HSCT. Read More

Pediatr Blood Cancer 2022 Jun 23:e29874. Epub 2022 Jun 23.

Department of Pediatric Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Cytometry B Clin Cytom 2022 Jun 23. Epub 2022 Jun 23.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China.

Background: ZNF384 rearrangement has been recently identified as a new subtype of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive studies clarifying immunophenotypic features and discriminating them from non-ZNF384 in adult BCP-ALL remain scarce to date.

Methods: Flow cytometric assessments were retrospectively performed in 43 patients with ZNF384 rearrangement, 45 with BCR-ABL1, 29 with KMT2A rearrangement and 44 with other BCP-ALL in the analysis cohort. Read More

Leuk Lymphoma 2022 Jun 23:1-3. Epub 2022 Jun 23.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Haematologica 2022 Jun 23. Epub 2022 Jun 23.

Princess Maxima Center for Pediatric Oncology, Utrecht.

Physiologic and pathogenic IL7-receptor (IL7R) induced signaling provokes glucocorticoid resistance in a subset of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. Activation of downstream STAT5 has been suggested to cause steroid resistance through upregulation of anti-apoptotic BCL2, one of its downstream target genes. Here, we demonstrate that isolated STAT5 signaling in various T-ALL cell models is insufficient to raise cellular steroid resistance despite upregulation of BCL2 and BCL-XL. Read More

Expert Rev Anticancer Ther 2022 Jun 22. Epub 2022 Jun 22.

A/31, 65-D, Bafna Courts, West Ponnurangam Road, RS Puram, Coimbatore, India.

Introduction: AYA-ALL differs from pediatric ALL in terms of clinical, biological, psychosocial factors and access to care and has an inferior outcome. It is now being recognized that pediatric-inspired protocols are superior to adult protocols for this cohort, but given the lack of randomized trials, several questions remain unanswered.

Areas Covered: In this review, we discuss how AYA-ALL is different from the pediatric ALL population, compare AYA ALL with ALL in middle and older age adults, review the studies that have enrolled the AYA cohort, summarize risk-stratified and response-adapted approaches, describe the biological subtypes, and review the novel agents/approaches under evaluation. Read More

Front Oncol 2022 6;12:846573. Epub 2022 Jun 6.

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Suzhou, China.

Early T-cell precursor (ETP) lymphoblastic leukemia/lymphoma is a high-risk T lymphoblastic leukemia/lymphoma (T-ALL/LBL) subgroup. We performed a real-world multicenter study to explore the clinical characteristics and prognosis of adolescent and young adults (AYA) and older adult ETP leukemia/lymphoma. A total of 103 patients with ETP-ALL/LBL in five centers in China between January 2016 and February 2021 were included in this study. Read More

Pan Afr Med J 2022 29;41:257. Epub 2022 Mar 29.

Service d'Hématologie Clinique, Centre Hospitalier Universitaire Mohammed VI Marrakech, Faculté de Médecine et de Pharmacie, Université Cadi Ayyad, Marrakech, Maroc.

Malignant hypercalcaemia is a metabolic emergency. Its association with solid tumors is common, whereas it has been rarely described in patients with malignant hemopathies other than multiple myeloma and T-cell leukemias/T-cell lymphomas associated with lymphotropic virus type I (HTLV-I). We here report the case of a female patient with acute lymphoblastic leukemia revealed by malignant hypercalcaemia and pathological fracture of the humerus. Read More

Front Immunol 2022 6;13:915590. Epub 2022 Jun 6.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking-Tsinghua Center for Life Science, Research Unit of Key Technique for Diagnosis and Treatment of Hematologic Malignancies, Chinese Academic of Medical Sciences, Beijing, China.

Measurable residual disease (MRD) positivity before haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an independent prognostic factor in determining outcomes in patients with B-cell acute lymphoblastic leukemia (ALL). In this study, we conducted a parallel comparison of the efficacy and safety in patients with suboptimal MRD response after reinduction who underwent haplo-HSCT after chimeric antigen receptor T-cell (CAR-T) therapy or chemotherapy. Forty B-cell ALL patients who relapsed after first-line chemotherapy and with an MRD ≥0. Read More

Front Pediatr 2022 6;10:831229. Epub 2022 Jun 6.

Department of Paediatric Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Objective: To investigate the correlation between gene mutations and glucocorticoid resistance in pediatric acute lymphoblastic leukemia (ALL).

Methods: A total of 71 children with ALL admitted to our center between September 2019 and September 2021 were enrolled. DNA obtained from bone marrow or peripheral blood samples at initial diagnosis was used for genetic testing whole exome sequencing. Read More

Pediatr Blood Cancer 2022 Jun 22:e29873. Epub 2022 Jun 22.

Department of Pediatrics, University of Colorado Anschutz Medical Campus and Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, Colorado, USA.

BMJ Case Rep 2022 Jun 22;15(6). Epub 2022 Jun 22.

Hematology and Oncology, VA West Los Angeles Medical Center, Los Angeles, California, USA.

Although patients with multiple myeloma (MM) have improved survival with current therapies, there remains a long-term risk of treatment-associated second primary malignancies. We present a case of a patient with IgG kappa MM undergoing treatment for relapsed disease who was noted to have progressive pancytopenia. For his MM, he had previously undergone autologous stem cell transplant with high-dose melphalan and had received immunomodulatory (IMiD) agents in induction, maintenance and relapse regimens. Read More