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philadelphia chromosome-positive acute lymphoblastic leukemia

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https://www.readbyqxmd.com/read/27913529/ph-like-acute-lymphoblastic-leukemia
#1
Thai Hoa Tran, Mignon L Loh
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a newly identified high-risk (HR) B-lineage ALL subtype, accounting for ∼15% of children with National Cancer Institute-defined HR B-ALL. It occurs more frequently in adolescents and adults, having been reported in as much as 27% of young adults with ALL between 21 and 39 years of age. It exhibits adverse clinical features, confers a poor prognosis, and harbors a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, making it amenable to treatment with tyrosine kinase inhibitor (TKI) therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#2
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894622/a-case-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-partial-trisomy-of-chromosome-1q-involving-chromosome-13-as-the-acceptor-a-novel-cytogenetic-finding
#3
Mohit Bharadwaj, Anurag Sharma, Rahul Katara, Dinesh Pradhan, Raman Arora, Reena Mittal, Sambit K Mohanty
The Philadelphia (Ph) chromosome is infrequently found in acute lymphoblastic leukemia and is associated with poor prognosis. We present a case of Ph chromosome positive B cell-acute lymphoblastic leukemia with the partial trisomy of chromosome 1q involving chromosome 13 as the acceptor which has never been reported in the English literature. Jumping translocation (JT) of chromosome 1 is rare and is associated with disease progression and poor prognosis. Herein, we report the first case of Ph chromosome positive B cell-acute lymphoblastic leukemia with coexisting jumping translocation of chromosome 1 leading to trisomy of chromosome 1q...
September 4, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27890258/should-anyone-with-philadelphia-chromosome-positive-all-who-is-negative-for%C3%A2-minimal-residual-disease-receive-a-hematopoietic-stem-cell-transplant-in-first-remission
#4
REVIEW
Mark R Litzow
Outcomes for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in the pre-imatinib era were poor, particularly if patients did not receive an allogeneic hematopoietic stem cell transplant. This led to the recommendation that all patients with Ph+ ALL, if they were transplant candidates, should be transplanted. With the introduction of imatinib and subsequently other tyrosine kinase inhibitors, patient outcomes improved dramatically, raising the question of whether transplant in first complete molecular remission for these patients is really necessary...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#5
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821800/synergistic-effects-of-selective-inhibitors-targeting-the-pi3k-akt-mtor-pathway-or-nup214-abl1-fusion-protein-in-human-acute-lymphoblastic-leukemia
#6
Carolina Simioni, Simona Ultimo, Alberto M Martelli, Giorgio Zauli, Daniela Milani, James A McCubrey, Silvano Capitani, Luca M Neri
Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) accounts for 25-30% of adult ALL and its incidence increases with age in adults >40 years old. Irrespective of age, the ABL1 fusion genes are markers of poor prognosis and amplification of the NUP214-ABL1 oncogene can be detected mainly in patients with T-ALL. T cell malignancies harboring the ABL1 fusion genes are sensitive to many cytotoxic agents, but up to date complete remissions have not been achieved. The PI3K/Akt/mTOR signaling pathway is often activated in leukemias and plays a crucial role in leukemogenesis...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27803756/dasatinib-induced-pleural-effusion-chylothorax-an-option-to-consider
#7
Lucía Ferreiro, Esther San-José, Juan Suárez-Antelo, Luis Valdés
Dasatinib is a drug for treatment of oncogene fusion protein BCR-ABL-positive chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant/intolerant to imatinib. Pleural effusion (PE) is a common adverse effect, and in this context, we present four cases seen due to this cause. One of them is a chylothorax. The PE grade is variable, and the physiopathology is not well established, although a block in T-lymphocyte function or inhibition of platelet-derived growth factor receptor-β is suggested being involved...
October 2016: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/27799606/successful-reintroduction-of-blinatumomab-in-a-patient-with-relapsed-refractory-acute-lymphoblastic-leukemia-following-grade-4-cytokine-release-syndrome
#8
Bernard L Marini, Yihan Sun, Patrick W Burke, Anthony J Perissinotti
Relapsed/refractory acute lymphoblastic leukemia poses a clinical challenge due to its poor prognosis and lack of effective treatment. Blinatumomab, a novel immunotherapy, has demonstrated excellent efficacy in relapsed/refractory acute lymphoblastic leukemia; however, life-threatening toxicities such as cytokine release syndrome have been reported in pivotal clinical trials. In this report, we describe the safe reintroduction of blinatumomab in an adult patient with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia after experiencing grade 4 blinatumomab-induced cytokine release syndrome using a unique dosing strategy and a very diligent monitoring approach...
October 31, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27795510/mechanisms-of-drug-resistance-in-acute-lymphoblastic-leukemia
#9
Takeshi Inukai
Outcomes of patients with acute lymphoblastic leukemia (ALL) have improved dramatically with conventional chemotherapy consisting of multiple agents. However, considering the major impact of tyrosine kinase inhibitors in the treatment of Philadelphia chromosome-positive ALL, sensitivities to each chemotherapeutic agent must be appreciated in individual cases to further improve therapeutic outcomes of ALL patients. Recent advances in genome-wide association and comprehensive genetic mutation studies with next-generation sequencing enable the involvement of single nucleotide polymorphisms and acquired genetic mutations in the drug resistance of ALL to be evaluated...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27784350/-establishment-and-identification-of-mouse-model-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#10
Xue Wang, Na Qi, Sha Ma, Xu-Guang Song, Zhi-Ling Yan, Qing-Yun Wu, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To establish a mouse model of Ph(+) acute lymphoblastic leukemia (ALL) for providing a valuable tool to facilitate the researches on Ph(+) ALL. METHODS: CML-like mice were generated by transfection to bone marrow cells of BABL/c with Mig190 retrovirus. The Ph(+) ALL mouse model was established by infusion of sorted CML like mouse-derived BCR-ABL(+) B cells into the mice of same linege. Immonophenotypes, BCR-ABL transcription and expression of these leukemic cells were detected by flow cytometry, RT-PCR and Western blot respectively...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27781393/t-cell-rich-hla-haploidentical-hematopoietic-stem-cell-transplantation-for-relapsed-refractory-pediatric-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-without-posttransplant-tyrosine-kinase-inhibitor-therapy
#11
Hideki Sano, Kazuhiro Mochizuki, Mitsuko Akaihata, Shogo Kobayashi, Hitoshi Ohto, Atsushi Kikuta
Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT...
October 26, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27742477/acute-leukemia-characteristics-are-different-around-the-world-the-mexican-perspective
#12
David Gómez-Almaguer, Edson René Marcos-Ramírez, Efreen Horacio Montaño-Figueroa, Guillermo J Ruiz-Argüelles, Carlos Roberto Best-Aguilera, María Del Carmen López-Sánchez, Esperanza Barrera-Chairez, José Luis López-Arrollo, Christian Omar Ramos-Peñafiel, Andrés León-Peña, Elías Eugenio González-López, Perla Edith Rivas-García, Carlos Alberto Tellez-Hinojosa, Andrés Gómez-De León, José Carlos Jaime-Pérez
BACKGROUND: The incidence of acute leukemia (AL) has increased. Its prognosis is variable and depends on several baseline characteristics with a highly heterogeneous presentation. In Mexico, large-scale descriptive studies have not yet been published; the objective of this study was to analyze the initial basic characteristics of patients diagnosed with AL in our population. PATIENTS AND METHODS: In this multicenter, retrospective study, 1018 patients ≥ 16 years of age and diagnosed with AL between 2009 and 2014, were included...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27658493/screening-abl1-kinase-domain-mutations-in-patients-with-de-novo-philadelphia-chromosome-positive-ph-acute-lymphoblastic-leukemia-all
#13
He Li, Wanhua Zhang, Dongni Yi, Yuanxin Ye, Xueqiu Xiao
No abstract text is available yet for this article.
September 23, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27634020/the-persistence-of-minimal-residual-disease-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-we-know-it-s-bad-now-what
#14
Jessica T Leonard, Wendy Stock
No abstract text is available yet for this article.
November 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27629971/subdural-hematoma-associated-with-dasatinib-and-intrathecal-methotrexate-treatment-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#15
Hiroshi Ureshino, Atsujiro Nishioka, Kensuke Kojima, Haruna Kizuka, Haruhiko Sano, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Shinya Kimura
Dasatinib has been associated with an increased risk of bleeding, with the most prominent risk noted in patients with advanced-stage chronic myeloid leukemia and thrombocytopenia. We herein report two cases of Philadelphia chromosome-positive acute lymphoblastic leukemia in which a subdural hematoma developed in association with low-dose (40-50 mg/day) dasatinib treatment and lumbar puncture for intrathecal methotrexate injection. Both patients were in complete remission, with normal platelet counts and coagulation status...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27626518/rituximab-in-b-lineage-adult-acute-lymphoblastic-leukemia
#16
RANDOMIZED CONTROLLED TRIAL
Sébastien Maury, Sylvie Chevret, Xavier Thomas, Dominik Heim, Thibaut Leguay, Françoise Huguet, Patrice Chevallier, Mathilde Hunault, Nicolas Boissel, Martine Escoffre-Barbe, Urs Hess, Norbert Vey, Jean-Michel Pignon, Thorsten Braun, Jean-Pierre Marolleau, Jean-Yves Cahn, Yves Chalandon, Véronique Lhéritier, Kheira Beldjord, Marie C Béné, Norbert Ifrah, Hervé Dombret
BACKGROUND: Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. METHODS: We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point...
September 15, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27623040/ikaros-gene-deleted-b-cell-acute-lymphoblastic-leukemia-in-mexican-mestizos-observations-in-seven-patients-and-a-short-review-of-the-literature
#17
Guillermo José Ruiz-Delgado, Yahveth Cantero-Fortiz, Andrés Aurelio León-Peña, Mónica León-González, Ana Karen Nuñez-Cortés, Guillermo José Ruiz-Argüelles
BACKGROUND: In B-cell acute lymphoblastic leukemia, one of the most frequent cytogenetic alterations is the presence of the Philadelphia chromosome. Recently, newly identified genetic alterations have been studied, among them the IKZF1 deletion. IKZF1 encodes IKAROS, a zinc finger protein that plays an important role in hematopoiesis involving the regulation process of adhesion, cellular migration, and as a tumor suppressor. OBJECTIVE: We aimed to study the impact of IKAROS deletion in the evolution and prognosis of B-cell acute lymphoblastic leukemia...
July 2016: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/27582059/targeting-bcl-2-and-abl-lyn-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#18
Jessica T Leonard, Joelle S J Rowley, Christopher A Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E Spurgeon, Brian J Druker, Jeffrey W Tyner, Bill H Chang
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies...
August 31, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27548716/the-development-of-agents-targeting-the-bcr-abl-tyrosine-kinase-as-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-treatment
#19
Xavier Thomas, Maël Heiblig
In Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL...
November 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27537935/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-is-separated-into-two-subgroups-associated-with-survival-by-bcr-abl-fluorescence-in-situ-hybridization-of-segmented-cell-nuclei-report-from-a-single-institution
#20
Yoshimasa Kamoda, Kiyotaka Izumi, Futoshi Iioka, Takashi Akasaka, Fumihiko Nakamura, Chiyuki Kishimori, Katsuyo Tsuda, Katsuhiro Fukutsuka, Atsuko Okumura, Masahiko Hayashida, Hitoshi Ohno
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-...
2016: Acta Haematologica
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