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https://www.readbyqxmd.com/read/28819740/inotuzumab-ozogamicin-first-global-approval
#1
Yvette N Lamb
Intravenous inotuzumab ozogamicin (Besponsa(®); Pfizer) is an anti-CD22 monoclonal antibody-calicheamicin conjugate that binds to CD22-expressing tumour cells. Upon binding, the complex is internalised and the cytotoxic calicheamicin derivative is released inside the cell, inducing double-strand DNA breakage and subsequent cell death. In June 2017, the EMA granted inotuzumab ozogamicin approval as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL)...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28794907/rai1-overexpression-promotes-altered-circadian-gene-expression-and-dyssomnia-in-potocki-lupski-syndrome
#2
Sureni V Mullegama, Joseph T Alaimo, Michael D Fountain, Brooke Burns, Amanda Hebert Balog, Li Chen, Sarah H Elsea
Retinoic acid induced 1 ( RAI1 ) encodes a dosage-sensitive gene that when haploinsufficient results in Smith-Magenis syndrome (SMS) and when overexpressed results in Potocki-Lupski syndrome (PTLS). Phenotypic and molecular evidence illustrates that haploinsufficiency of RAI1 disrupts circadian rhythm through the dysregulation of the master circadian regulator, circadian locomotor output cycles kaput ( CLOCK) , and other core circadian components, contributing to prominent sleep disturbances in SMS. However, the phenotypic and molecular characterization of sleep features in PTLS has not been elucidated...
September 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28743306/detection-of-22-common-leukemic-fusion-genes-using-a-single-step-multiplex-qrt-pcr-based-assay
#3
Xiaodong Lyu, Xianwei Wang, Lina Zhang, Zhenzhu Chen, Yu Zhao, Jieying Hu, Ruihua Fan, Yongping Song
BACKGROUND: Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia...
July 25, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28731917/the-impact-of-iron-overload-in-acute-leukemia-chronic-inflammation-but-not-the-presence-of-nontransferrin-bound-iron-is-a-determinant-of-oxidative-stress
#4
Lale Olcay, Mustafa Serteser, Murat Kolay, Havva F Balci, Ülkü M Yildirim, Sibel A Tekgündüz, Tuncay Hazirolan, Yunus K Terzi
In the literature, studies on the oxidant effects of nontransferrin bound iron [NTBI (eLPI assay)] during chemotherapy of acute lymphoblastic leukemia and acute myeloblastic leukemia are lacking. We established NTBI and oxidative stress determinants (OSD), iron parameters, high-sensitive C-reactive protein (hs-CRP) levels, liver tests, cumulative chemotherapeutic doses, and transfused blood in 36 children with acute leukemia throughout chemotherapy. These parameters were determined at the beginning and end of chemotherapy blocks (11 time points) and in 20 healthy children using enzyme-linked immunosorbent assay, and colorimetric and fluorometric enzymatic methods...
August 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#5
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28698860/genomic-profiling-of-chronic-myelogenous-leukemia-basic-and-clinical-approach
#6
REVIEW
Aliasghar Keramatinia, Alireza Ahadi, Mohammad Esmaeil Akbari, Maryam Mohseny, Alireza Mosavi Jarahi, Narjes Mehrvar, Neda Mansouri, S A Mortazavi Tabatabaei, Abolfazl Movafagh
Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q(34):q(11)). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28684168/rnai-prodrugs-targeting-plk1-induce-specific-gene-silencing-in-primary-cells-from-pediatric-t-acute-lymphoblastic-leukemia-patients
#7
Iryna Kolosenko, Elin Edsbäcker, Ann-Charlotte Björklund, Alexander S Hamil, Oksana Goroshchuk, Dan Grandér, Steven F Dowdy, Caroline Palm-Apergi
Epidemiological studies of childhood leukemia survivors reveal an alarmingly high incidence of chronic health disabilities after treatment, therefore, more specific therapies need to be developed. Polo-like kinase 1 (Plk1) is a key player in mitosis and a target for drug development as it is upregulated in multiple cancer types. Small molecules targeting Plk1 are mainly ATP-competitors and, therefore, are known to elicit side effects due to lack of specificity. RNA interference (RNAi) is known for its high catalytic activity and target selectivity; however, the biggest barrier for its introduction into clinical use is its delivery...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#8
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28666906/craniospinal-irradiation-prior-to-stem-cell-transplant-for-hematologic-malignancies-with-cns-involvement-effectiveness-and-toxicity-after-photon-or-proton-treatment
#9
Jillian R Gunther, Ahmad R Rahman, Wenli Dong, Zeinab Abou Yehia, Partow Kebriaei, Gabriela Rondon, Chelsea C Pinnix, Sarah A Milgrom, Pamela K Allen, Bouthaina S Dabaja, Grace L Smith
PURPOSE/OBJECTIVE(S): Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT. METHODS AND MATERIALS: We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution...
May 10, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28655536/b-cell-identity-as-a-metabolic-barrier-against-malignant-transformation
#10
REVIEW
Lai N Chan, Markus Müschen
B-lineage and myeloid leukemia cells are often transformed by the same oncogenes, but have different biological and clinical characteristics. Although B-lineage acute lymphoblastic leukemia (B-ALL) cells are characterized by a state of chronic energy deficit, myeloid leukemia cells show abundant energy reserve. Interestingly, fasting has been demonstrated to inhibit selectively the development of B-ALL but not myeloid leukemia, further suggesting that lineage identity may be linked to divergent metabolic states in hematopoietic malignancies...
June 24, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28654149/young-adult-survivors-of-childhood-acute-lymphoblastic-leukemia-show-evidence-of-chronic-inflammation-and-cellular-aging
#11
Hany Ariffin, Mohamad Shafiq Azanan, Sayyidatul Syahirah Abd Ghafar, Lixian Oh, Kee Hie Lau, Tharshanadhevasheri Thirunavakarasu, Atiqah Sedan, Kamariah Ibrahim, Adelyne Chan, Tong Foh Chin, Fong Fong Liew, Shareni Jeyamogan, Erda Syerena Rosli, Rashidah Baharudin, Tsiao Yi Yap, Roderick Skinner, Su Han Lum, Pierre Hainaut
BACKGROUND: Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation. METHODS: Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls...
June 27, 2017: Cancer
https://www.readbyqxmd.com/read/28641661/-clinical-and-pathologic-features-of-myeloid-sarcoma
#12
Ya-Jun Jiang, Hong-Xia Wang, Wan-Chuan Zhuang, Hao Chen, Chang Zhang, Xiu-Mei Li, Gui-Hua Zhu, Yao He
OBJECTIVE: To explore the clinicopathologic features, differential diagnosis and therapy of myeloid sarcoma. METHODS: The clinical data including clinical manifestations, laboratorial tests, histopathologicical examination, immunohistochemistry and clinical prognosis of 10 patients with myeloid sarcoma were analyzed retrospectively. Among 10 patients, 5 male and 5 female, aged 23 to 71 years old (median = 36 years). RESULTS: 2 cases of myeloid sarcoma were secondary from chronic myeloid leukemia, and 1 cases of myeloid sarcoma occurred after the allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia, and the others lacked the anamnesis of malignancies...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641145/lack-of-association-between-deletion-polymorphism-of-bim-gene-and-in-vitro-drug-sensitivity-in-b-cell-precursor-acute-lymphoblastic-leukemia
#13
Meixian Huang, Kunio Miyake, Keiko Kagami, Masako Abe, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Kumiko Goi, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Nobutaka Kiyokawa, Kanji Sugita, Takeshi Inukai
A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy...
June 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28614903/thiotepa-based-conditioning-versus-total-body-irradiation-as-myeloablative-conditioning-prior-to-allogeneic-stem-cell-transplantation-for-acute-lymphoblastic-leukemia-a-matched-pair-analysis-from-the-acute-leukemia-working-party-of-the-european-society-for
#14
Sandra Eder, Jonathan Canaani, Eric Beohou, Myriam Labopin, Miguel A Sanz, William Arcese, Reuven Or, Juergen Finke, Agostino Cortelezzi, Dietrich Beelen, Jakob Passweg, Gerard Socié, Gunhan Gurman, Mahmoud Aljurf, Matthias Stelljes, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
The optimal conditioning regimen to employ before hematopoieitic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while Cy/TBI is the most commonly used myeloablative regimen, there are concerns regarding long term toxicity for patients conditioned with this regimen. Thiotepa based conditioning is an emerging radiation free regimen with recent publications indicative of comparable clinical outcomes to TBI based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n=180) with those receiving Cy/TBI conditioning (n=540)...
June 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28600336/diagnosis-and-classification-of-hematologic-malignancies-on-the-basis-of-genetics
#15
REVIEW
Justin Taylor, Wenbin Xiao, Omar Abdel-Wahab
Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia...
July 27, 2017: Blood
https://www.readbyqxmd.com/read/28592129/allogeneic-stem-cell-transplantation-after-fludarabine-melphalan-and-thymoglobulin-followed-by-early-withdrawal-of-prophylactic-immunosuppression-in-patients-with-acute-lymphoblastic-leukemia-update-of-single-center-study
#16
L Raida, A Kuba, Z Rusinakova, R Szotkowska, I Skoumalova, E Faber, T Szotkowski, P Rohon, J Hubacek, K Indrak, Z Pikalova, M Jarosova, M Divoka, K Langova, T Papajik
Presented are updated results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 25 adult patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) after a reduced intensity conditioning (RIC) combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg or recently 4.0 mg/kg) followed by early initiation of reduction and withdrawal of prophylactic posttransplant immunosuppression. The median post-transplant follow-up was 32 (range, 4-87) months. Stable engraftment of donor's hematopoiesis was achieved in all patients...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28586310/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#17
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28558762/unmanipulated-haploidentical-stem-cell-transplantation-in-adults-with-acute-lymphoblastic-leukemia-a-study-on-behalf-of-the-acute-leukemia-working-party-of-the-ebmt
#18
Nicole Santoro, Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Fabio Ciceri, Zafer Gülbaş, He Huang, Boris Afanasyev, William Arcese, Depei Wu, Yener Koc, Johanna Tischer, Stella Santarone, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
BACKGROUND: Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. METHODS: We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. RESULTS: Median age at haplo-SCT was 32 years and median follow-up, 31 months...
May 30, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28552244/ca-2-signalling-underlying-pancreatitis
#19
REVIEW
J V Gerasimenko, S Peng, T Tsugorka, O V Gerasimenko
In spite of significant scientific progress in recent years, acute pancreatitis (AP) is still a dangerous and in up to 5% of cases deadly disease with no specific cure. It is self-resolved in the majority of cases, but could result in chronic pancreatitis (CP) and increased risk of pancreatic cancer (PC). One of the early events in AP is premature activation of digestive pro-enzymes, including trypsinogen, inside pancreatic acinar cells (PACs) due to an excessive rise in the cytosolic Ca(2+) concentration, which is the result of Ca(2+) release from internal stores followed by Ca(2+) entry through the store operated Ca(2+) channels in the plasma membrane...
May 18, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28551329/myeloproliferative-neoplasms-with-t-8-22-p11-2-q11-2-bcr-fgfr1-a-meta-analysis-of-20-cases-shows-cytogenetic-progression-with-b-lymphoid-blast-phase
#20
Ximena Montenegro-Garreaud, Roberto N Miranda, Alexandra Reynolds, Guilin Tang, Sa A Wang, Mariko Yabe, Wei Wang, Lianghua Fang, Carlos E Bueso-Ramos, Pei Lin, L Jeffrey Medeiros, Xinyan Lu
Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of the FGFR1 is ZMYM2 and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with the FGFR1 and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia (CML) or very rarely, with B lymphoblastic leukemia (B-ALL)...
May 24, 2017: Human Pathology
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