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Ph+ acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#1
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
#2
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
#3
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
#4
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) versus 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 versus SOC. Response rates, event free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER...
June 20, 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
#5
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
#6
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
#7
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...
June 13, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28592975/prognostic-factors-and-treatment-of-pediatric-acute-lymphoblastic-leukemia
#8
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
#9
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
#10
S T 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 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
#11
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
#12
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
#13
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)...
May 26, 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
#14
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
#15
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
https://www.readbyqxmd.com/read/28446276/-clinical-features-and-prognostic-factors-of-children-with-acute-lymphoblastic-leukemia-in-high-risk-group
#16
Shu-Hong Zhang, Fen-Yan An, Ji-Xin Xu, Ling-Jun Kong, Hai-Long He, Yi-Huan Chai, Wen-Lin Zhao
OBJECTIVE: To explore the clinical features and prognostic factors of pediatric acute lymphoblastic leukemia (ALL) in high-risk (HR) group. METHODS: A total of 421 children with ALL in the Children's Hospital of Soochow University from August 2008 to March 2013 were diagnosed and treated according to the Chinese Children Leukemia Group (CCLG)-2008 Protocol. Among different risk-groups, 148 cases were stratified into the low-risk group and 191 cases were included in the moderate-risk group...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#17
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#18
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#19
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419558/age-but-not-philadelphia-positivity-impairs-outcome-in-older-elderly-patients-with-acute-lymphoblastic-leukemia-in-sweden
#20
Piotr Kozlowski, Emma Lennmyr, Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Holger Karbach, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åström, Heléne Hallböök
OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype...
April 18, 2017: European Journal of Haematology
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