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Ph+ acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#1
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/28711932/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#2
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28702060/oral-health-status-salivary-ph-status-and-streptococcus-mutans-counts-in-dental-plaques-and-saliva-of-children-with-acute-lymphoblastic-leukemia
#3
Romina Mazaheri, Ebrahim Jabbarifar, Elnaz Ghasemi, Elahe Akkafzadeh, Elmira Poursaeid
BACKGROUND: Acute lymphoblastic leukemia (ALL), accounting for 23% of all malignancies in children, is the most prevalent pediatric malignancy. This study compared dental caries, oral hygiene status, salivary pH, and Streptococcus mutans counts in dental plaques and saliva of children with leukemia with those of healthy controls. MATERIALS AND METHODS: This case-control cross-sectional study assessed 32 children with ALL and 32 healthy children (4-9-year-old) for gingival bleeding index (GBI), decayed, missing, and filled/decayed, missing, and filled surfaces (DMF/dmfs), and plaque index (PI)...
May 2017: Dental Research Journal
https://www.readbyqxmd.com/read/28683103/combination-therapeutics-of-nilotinib-and-radiation-in-acute-lymphoblastic-leukemia-as-an-effective-method-against-drug-resistance
#4
Kamran Kaveh, Yutaka Takahashi, Michael A Farrar, Guy Storme, Marcucci Guido, Jamie Piepenburg, Jackson Penning, Jasmine Foo, Kevin Z Leder, Susanta K Hui
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28654842/haploidentical-hematopoietic-stem-cell-transplantation-for-pediatric-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-the-imatinib-era
#5
Huan Chen, Kai-Yan Liu, Lan-Ping Xu, Yu-Hong Chen, Xiao-Hui Zhang, Yu Wang, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Xiao-Jun Huang
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important curative option for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have a poor response to chemotherapy plus imatinib. For such children, if there are no matched related or unrelated donors, alternative donor transplantation may be a choice. The role of haploidentical donor (HID) HSCT in pediatric patients with Ph+ ALL has not been reported. The study population included pediatric patients with Ph+ ALL who underwent HID-HSCT...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#6
Peter M Alexander, David L Caudell, Gregory L Kucera, Kristin M Pladna, Timothy S Pardee
Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable...
2017: PloS One
https://www.readbyqxmd.com/read/28641630/-sdf-1%C3%AE-cxcr4-mediated-drug-resistance-can-be-reversed-by-ibrutinib-in-acute-lymphoblastic-leukemia
#7
Yuan-Yuan Hu, Shan-Dong Tao, Jing-Jing Ma, Li-Tao Zhou, Yue Chen, Liang Yu
OBJECTIVE: To explore the effect of Ibrutinib on the chemoresistance mediated by SDF-1α/CXCR4 axis in ALL cells. METHODS: Flow cytometry was used to detect the apoptosis of cell line and expression of surface membrane CXCR4, Western blot was used to determine the expression level of CXCR4, ERK and Bcl-xL proteins, qPCR was used to assay the mRNA level of CXCR4. RESULTS: Ibrutinib enhanced the apoptosis induced by adriamycin(ADR) (17.100±4...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641623/-analysis-of-clinical-characteristics-and-therapeutic-efficacy-in-61-adult-patients-with-acute-lymphoblastic-leukemia
#8
Xiao-Ping Zhang, Bao-An Chen, Zheng Ge, Ran Liu, Xiao-Yan Ma, Chong Gao
OBJECTIVE: To investigate the clinical characteristics and curative effect in 61 adult patients with acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 61 patients (≥15 years old) with ALL enrolled from January 2010 to December 2014 were studied retrospectively. The relationship between clinical characteristics and curative effect was analyzed. The univariate and multivariate analyses related with the overall survival (OS) and disease free survival (DFS) were conducted by using the method of COX regression analysis...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28631497/cost-effectiveness-of-blinatumomab-versus-salvage-chemotherapy-in-relapsed-or-refractory-philadelphia-chromosome-negative-b-precursor-acute-lymphoblastic-leukemia-from-a-us-payer-perspective
#9
Thomas E Delea, Jordan Amdahl, Diana Boyko, May Hagiwara, Zachary F Zimmerman, Janet L Franklin, Ze Cong, Guy Hechmati, Anthony Stein
OBJECTIVE: To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. METHODS: The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC...
July 11, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28616912/-the-roles-of-glut5-in-imatinib-resistance-in-the-ph-acute-lymphoblastic-leukemia-cell
#10
Tian-You Yan, Duo-Lan Naren, Yu-Ping Gong
OBJECTIVES: To explore the possible roles of glucose transport 5 (Glut5) in imatinib resistance in the Ph(+) acute lymphoblastic leukemia cell (Ph(+) ALL). METHODS: The gene chip technique was used to detect different gene expression between Ph(+) ALL cell line SUP-B15/R (imatinib resistant cell line) and SUP-B15/S (imatinib sensitive cell line), the gene of solute carrier family 2 member 5 (SLC2A5) and its coded protein Glut5 were screened out and were reconfirmed by qPCR and Western blot assay...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28612529/-the-mechanism-of-combination-using-mtorc1-2-inhibitor-and-imatinib-to-suppress-cell-proliferation-of-ph-all-cell-line
#11
Jia-Hui Wu, Fang-Fang Shi, Yu-Ping Gong, Rui Shi
OBJECTIVES: To investigate the anti-leukemia effect and mechanism of mTORC1/2 inhibitor PP242 combined with imatinib (IM) on the proliferation of Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: SUP-B15 cell line was treated with PP242, imatinib (IM), or PP242 plus IM for 72 h, IC50 values (the concentration of drug required to kill 50% of the cells) and the combination index (CI ) of synergistic cytotoxicity was determined using MTT methods...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28608730/novel-therapy-for-childhood-acute-lymphoblastic-leukemia
#12
Raoul Santiago, Stéphanie Vairy, Daniel Sinnett, Maja Krajinovic, Henrique Bittencourt
During recent decades, the prognosis of childhood acute lymphoblastic leukemia (ALL) has improved dramatically, nowadays, reaching a cure rate of almost 90%. These results are due to a better management and combination of old therapies, refined risk-group stratification and emergence of minimal residual disease (MRD) combined with treatment's intensification for high-risk subgroups. However, the subgroup of patients with refractory/relapsed ALL still presents a dismal prognosis indicating necessity for innovative therapeutic approaches...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28592975/prognostic-factors-and-treatment-of-pediatric-acute-lymphoblastic-leukemia
#13
REVIEW
Jae Wook Lee, Bin Cho
The event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL) has shown remarkable improvement in the past several decades. In Korea also, a recent study showed 10-year EFS of 78.5%. Much of the improved outcome for pediatric ALL stems from the accurate identification of prognostic factors, the designation of risk group based on these factors, and treatment of appropriate duration and intensity according to risk group, done within the setting of cooperative clinical trials. The schema of first-line therapy for ALL remains mostly unchanged, although many groups have now reported on the elimination of cranial irradiation in all patients with low rates of central nervous system relapse...
May 2017: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28581459/the-evolving-role-of-chemotherapy-and-hematopoietic-cell-transplants-in-ph-positive-acute-lymphoblastic-leukemia-in-adults
#14
REVIEW
M R Litzow, A K Fielding, S M Luger, E Paietta, Y Ofran, J M Rowe, A H Goldstone, M S Tallman, H M Lazarus
The introduction of the tyrosine kinase inhibitors (TKI) into the treatment of patients with Ph or BCR-ABL1-positive acute lymphoblastic leukemia has revolutionized the treatment of this poor prognosis acute leukemia. The combination of TKI with chemotherapy has improved response rates and allowed more patients to proceed to allogeneic hematopoietic cell transplant (alloHCT). Older patients have excellent responses to TKI and corticosteroids or in combination with minimal chemotherapy. This raises the question as to whether patients require full-intensity chemotherapy with TKI to achieve molecular remissions...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28579617/hdac1-2-inhibition-and-doxorubicin-impair-mre11-dependent-dna-repair-and-disc-to-override-bcr-abl1-driven-dsb-repair-in-philadelphia-chromosome-positive-b-cell-precursor-acute-lymphoblastic-leukemia
#15
S Tharkar-Promod, D P Johnson, S E Bennett, E M Dennis, B G Banowsky, S S Jones, J R Shearstone, S N Quayle, C Min, M Jarpe, T Mosbruger, A D Pomicter, R R Miles, W Y Chen, K N Bhalla, P A Zweidler-McKay, D C Shrieve, M W Deininger, M B Chandrasekharan, S Bhaskara
Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL) expressing BCR-ABL1 oncoprotein is a major subclass of ALL with poor prognosis. BCR-ABL1-expressing leukemic cells are highly dependent on double-strand break (DSB) repair signals for their survival. Here we report that a first-in-class HDAC1,2 selective inhibitor and doxorubicin (a hyper-CVAD chemotherapy regimen component) impair DSB repair networks in Ph+ B-cell precursor ALL cells using common as well as distinct mechanisms...
June 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28566433/mtorc1-inhibition-induces-resistance-to-methotrexate-and-6-mercaptopurine-in-ph-and-ph-like-b-all
#16
Thanh-Trang T Vo, Jong-Hoon S Lee, Duc Nguyen, Brandon Lui, William Pandori, Andrew Khaw, Sharmila Mallya, Mengrou Lu, Markus Müschen, Marina Konopleva, David A Fruman
Elevated activity of the mechanistic target of rapamycin (mTOR) is associated with poor prognosis and higher incidence of relapse in B-cell acute lymphoblastic leukemia (B-ALL). Thus, ongoing clinical trials are testing mTOR inhibitors in combination with chemotherapy in B-ALL. However, the combination of mTOR inhibitors with standard of care chemotherapy drugs has not been studied extensively in high risk B-ALL subtypes. Therefore, we tested whether mTOR inhibition can augment the efficacy of current chemotherapy agents in Ph(+) and Ph-like B-ALL models...
May 31, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28554259/frequency-and-prognostic-significance-of-additional-cytogenetic-abnormalities-to-the-philadelphia-chromosome-in-young-and-older-adults-with-acute-lymphoblastic-leukemia
#17
Cristina Motlló, Josep-Maria Ribera, Mireia Morgades, Isabel Granada, Pau Montesinos, Santiago Mercadal, José González-Campos, María-José Moreno, Pere Barba, Marta Cervera, Manuel Barrios, Andrés Novo, Teresa Bernal, Jesús-María Hernández-Rivas, Eugenia Abella, María-Luz Amigo, Mar Tormo, Rodrigo Martino, Esperanza Lavilla, Juan Bergua, Alfons Serrano, Daniel García-Belmonte, Ramon Guàrdia, Javier Grau, Evarist Feliu
About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining...
May 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28550450/abcc4-functional-snp-in-the-3-splice-acceptor-site-of-exon-8-g912t-is-associated-with-unfavorable-clinical-outcome-in-children-with-acute-lymphoblastic-leukemia
#18
Hamzeh Mesrian Tanha, Soheila Rahgozar, Marjan Mojtabavi Naeini
OBJECTIVES: ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T; K304N) is located in the 3' splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim of this study was to investigate the prognostic value of rs2274407 in childhood ALL and its possible functional effect on MRP4. METHODS: ABCC4 G912T SNP was genotyped in 145 Iranian Philadelphia-negative (Ph(-)) children with ALL using modified tetra-primer ARMS PCR and evaluated for possible association with 3-year disease-free survival (3DFS)...
July 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#19
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28454362/growth-of-tyrosine-kinase-inhibitor-resistant-philadelphia-positive-acute-lymphoblastic-leukemia-role-of-bone-marrow-stromal-cells
#20
Cheng Zhang, Xi Zhang, Shi-Jie Yang, Xing-Hua Chen
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph(+) ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8...
April 2017: Oncology Letters
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