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William J Archibald, Philip J Meacham, AnnaLynn M Williams, Andrea M Baran, Adrienne I Victor, Paul M Barr, Deepak M Sahasrahbudhe, Clive S Zent
Melanoma is significantly more common and is associated with a poorer prognosis in patients with an underlying B-cell malignancy. This study reports on the management of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and a subsequent diagnosis of melanoma. In the Wilmot Cancer Institute CLL cohort, which includes 470 patients followed for 2849 person-years, 18 patients (3.8%) developed 22 melanomas. Fourteen melanomas were invasive, a significantly higher rate as compared with the age and sex matched general population (standardized incidence ratio [SIR] 6...
July 6, 2018: Leukemia Research
M Niedźwiecki, O Budziło, M Zieliński, E Adamkiewicz-Drożyńska, L Maciejka-Kembłowska, T Szczepański, P Trzonkowski
CD4+ CD25high CD127low/- FoxP3 + regulatory T cells (Tregs) are currently under extensive investigation in childhood acute lymphoblastic leukemia (ALL) and in other human cancers. Usually, Treg cells maintain the immune cell homeostasis. This small subset of T cells has been, in fact, considered to be involved in the pathogenesis of autoimmune diseases and progression of acute and chronic leukemias. However, whether Treg dysregulation in CLL and ALL plays a key role or it rather represents a simple epiphenomenon is still a matter of debate...
2018: Journal of Immunology Research
Emanuela Rosati, Stefano Baldoni, Filomena De Falco, Beatrice Del Papa, Erica Dorillo, Chiara Rompietti, Elisa Albi, Franca Falzetti, Mauro Di Ianni, Paolo Sportoletti
Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL...
2018: Frontiers in Oncology
Peter Dreger, Paolo Ghia, Johannes Schetelig, Michel van Gelder, Eva Kimby, Mauricette Michallet, Carol Moreno, Tadeusz Robak, Stephan Stilgenbauer, Emili Montserrat
High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance ( TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PI), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by TP53 abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with TP53 aberrations, but fully responsive to PI...
July 11, 2018: Blood
Xixi Xiang, Yu-Ping Wang, Hongbao Cao, Xi Zhang
Objective To investigate whether previously curated chronic lymphocytic leukemia (CLL) risk genes could be leveraged in gene marker selection for the diagnosis and prediction of CLL. Methods A CLL genetic database (CLL_042017) was developed through a comprehensive CLL-gene relation data analysis, in which 753 CLL target genes were curated. Expression values for these genes were used for case-control classification of four CLL datasets, with a sparse representation-based variable selection (SRVS) approach employed for feature (gene) selection...
January 1, 2018: Journal of International Medical Research
Muhammad Omar, Vasantha Gali, Arvin Santos, Mark Huber, Nishant Parmar
Dysproteinemia is excessive production of immunoglobulins from clonal proliferation of plasma or B cells. Cryoglobulins are a special group of immunoglobulins that precipitate below 37 degrees C. Type 1 cryoglobulinemia consists mostly of IgM and IgG that infrequently leads to glomerulonephritis. In these situations, an underlying malignancy is even rare with only 21 cases described so far with only four having chronic lymphocytic leukemia (CLL). We present a case of a 68-year-old male admitted with hypertension and kidney dysfunction who upon work up was found to have CLL...
February 2018: South Dakota Medicine: the Journal of the South Dakota State Medical Association
Rafet Eren, Elif Suyanı
No abstract text is available yet for this article.
July 9, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Talal Hilal, Jeffrey A Betcher, Jose F Leis
PURPOSE OF REVIEW: Small molecule tyrosine kinase inhibitors (TKIs) and BCL2 inhibitors are oral targeted therapies that have changed the treatment approach to patients with chronic lymphocytic leukemia (CLL). The aim of this review is to summarize the relevant literature on the economic impact of oral novel therapies for the treatment of CLL and discuss the underlying factors and suggested solutions for high drug prices. RECENT FINDINGS: The cost of therapy for CLL has increased substantially since the introduction of oral therapies...
July 7, 2018: Current Hematologic Malignancy Reports
Jing Chang, Haiyong Peng, Brian C Shaffer, Sivasubramanian Baskar, Ina C Wecken, Matthew G Cyr, Gustavo J Martinez, Jo Soden, Jim Freeth, Adrian Wiestner, Christoph Rader
Although the five-year survival rate of chronic lymphocytic leukemia (CLL) patients has risen to >80%, the only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (alloHSCT). To identify possible new monoclonal antibody (mAb) drugs and targets for CLL, we previously developed a phage display-based human mAb platform to mine the antibody repertoire of patients who responded to alloHSCT. We had selected a group of highly homologous post-alloHSCT mAbs that bound to an unknown CLL cell surface antigen...
July 6, 2018: Cancer Immunology Research
Kyle Crassini, Yandong Shen, Michael O'Dwyer, Michael O'Neill, Richard Christopherson, Stephen Mulligan, O Giles Best
Despite significant advances in treatment, chronic lymphocytic leukaemia (CLL) remains an incurable disease. Ibrutinib and idelalisib, which inhibit Bruton Tyrosine kinase (BTK) and phosphoinositol-3 (PI3) kinase-δ respectively, have become important treatment options for the disease and demonstrate the potential of targeting components of the B-cell receptor-signalling pathway. IBL-202 is a dual inhibitor of the PIM and PI3 kinases. Synergy between the pan-PIM inhibitor, pPIMi, and idelalisib against a range of haematological cell lines and primary CLL cells supports the rationale for preclinical studies of IBL-202 in CLL...
July 5, 2018: British Journal of Haematology
Filipa Mousinho, Tatiana Mendes, Paula Sousa E Santos, Maria João Acosta, José Pereira, Maria Arroz, Cândido Silva, Ana Paula Azevedo, Rita Oliveira, Martinha Chorão, Fernando Lima
Early-stage chronic lymphocytic leukemia (CLL) with neurologic involvement is a rare condition and should require a careful follow-up. Although no standard protocol exists for this condition, intrathecal chemotherapy, combined with systemic chemoimmunotherapy, has been used previously. This case describes the treatment of a patient with CLL and symptomatic compromise of the central nervous system. Our results suggest that a combination of chemotherapy, radiotherapy, and ibrutinib, administered sequentially over a 2-year period, led to a near-complete resolution of the cerebral spinal fluid neoplastic infiltration...
2018: Case Reports in Hematology
Longtao Wu, Giovanna M Bernal, Kirk E Cahill, Peter Pytel, Carrie A Fitzpatrick, Heather Mashek, Ralph R Weichselbaum, Bakhtiar Yamini
The response of patients with gliomas to alkylating chemotherapy is heterogeneous. However, there are currently no universally accepted predictors of patient response to these agents. We identify the nuclear factor κB (NF-κB) co-regulator B cell CLL/lymphoma 3 (BCL-3) as an independent predictor of response to temozolomide (TMZ) treatment. In glioma patients with tumors that have a methylated O 6 -methylguanine DNA methyltransferase ( MGMT ) promoter, high BCL-3 expression was associated with a poor response to TMZ...
July 4, 2018: Science Translational Medicine
Di Wu, Jiankuo Du, Yan Zhang, Yunming Su, Hongfeng Zhang
Aim: This study was conducted to investigate the anti-tumor effects of the Chinese traditional herb phenolic alkaloids of menispermum dauricum (PAMD) on gastric cancer both in vitro and in vivo. Materials and Methods: Cell apoptosis was detected in cultured SGC-7901 cells after administration of a different dose of PAMD. Gastric cancer model was established by single i.p. injection of SGC-7901 cells in the mice (n = 60). Then, animals were received high dose (20 mg/kg), medial dose (10 mg/kg), and low dose (5 mg/kg) of PAMD...
June 2018: Journal of Cancer Research and Therapeutics
Eduardo S Cantú, Henry Dong, David R Forsyth, Froilan P Espinoza, Peter R Papenhausen
Conventional cytogenetic and routine I-FISH (interphase fluorescence in-situ hybridization) studies periodically present discrepant results on the same sample calling into question their validity. Generally it is expected that these tests confirm each other, otherwise there is concern that they may represent laboratory error. We present data showing that these discrepant results are rarely due to laboratory error, and that M-FISH (metaphase fluorescence in-situ hybridization) can usually reconcile them by identifying the nature of these differences...
May 2018: Annals of Clinical and Laboratory Science
Silvia Mele, Stephen Devereux, Andrea G Pepper, Elvira Infante, Anne J Ridley
CD38 is a transmembrane exoenzyme that is associated with poor prognosis in chronic lymphocytic leukemia (CLL). High CD38 levels in CLL cells are linked to increased cell migration, but the molecular basis is unknown. CD38 produces nicotinic acid adenine dinucleotide phosphate and adenosine 5'-diphosphate-ribose, both of which can act to increase intracellular Ca2+ levels. Here we show that CD38 expression increases basal intracellular Ca2+ levels and stimulates CLL cell migration both with and without chemokine stimulation...
July 10, 2018: Blood Advances
Francesca R Mauro, Maria D Caputo, Serena Rosati, Sara Pepe, Daniela De Benedittis, Maria L De Luca, Robin Foà
In recent years, innovative mechanism-based drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia [CLL] and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway and the Bcl-2 anti-apoptotic protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, treatment with ibrutinib, idelalisib and venetoclax is associated with unique side effects...
July 3, 2018: Expert Review of Hematology
Bing Zheng, Shang-Fan Yu, Geoffrey Del Rosario, Steven R Leong, Genee Y Lee, Rajesh Vij, Cecilia P C Chiu, Wei-Ching Liang, Yan Wu, Cecile Chalouni, Jack Sadowsky, Vanessa M Clark, Angela Hendricks, Kirsten Achilles Poon, Yu-Waye Chu, Thomas H Pillow, M M Schutten, John A Flygare, Andrew G Polson
PURPOSE: The treatment of acute myeloid leukemia (AML) has not significantly changed in 40 years. Cytarabine and anthracycline‑based chemotherapy induction regimens (7 + 3) remain the standard of care, and most patients have poor long-term survival. The re-approval of Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), has demonstrated ADCs as a clinically validated option to enhance the effectiveness of induction therapy. We are interested in developing a next generation ADC for AML to improve upon the initial success of Mylotarg...
June 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Csilla Kriston, Márk Plander, Ágnes Márk, Anna Sebestyén, Edina Bugyik, András Matolcsy, Gábor Barna
CD49d and CXCR4 are key determinants of interactions between chronic lymphocytic leukemia (CLL) tumor cells and their microenvironment. In this study, we investigated the effect of CD49d and CXCR4 expressions on survival of CLL cells. Primary CLL cells were cultured with CD49d ligand, VCAM-1, or bone marrow stromal cells (BMSCs); then, apoptosis and immunophenotype analyses were performed. VCAM-1 treatment could not induce direct apoptosis protection or immunophenotype change on the CD49d-expressing CLL cells, but resulted in actin reorganization...
June 28, 2018: Annals of Hematology
Lokesh Shahani
Histoplasma microconidia when inhaled are presented in antigenic form to T cells, limiting the extent of infection; however, defects in cellular immunity results in disseminated disease. Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder resulting in functionally impaired lymphocytes, predisposing patients to various opportunistic infections. The author reports a recently treated patient with CLL presenting with constitutional symptoms accompanied by hepatosplenomegaly and diffuse adenopathy...
June 28, 2018: BMJ Case Reports
Daniel Prieto, Noé Seija, Angimar Uriepero, Thais Souto-Padron, Carolina Oliver, Victoria Irigoin, Cecilia Guillermo, Marcelo A Navarrete, Ana Inés Landoni, Guillermo Dighiero, Raúl Gabus, Mirta Giordano, Pablo Oppezzo
Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that did or did not express LPL mRNA. Our results show that LPL protein is differently located in CLL cells depending on whether it is incorporated from the extracellular medium in mutated CLL or generated de novo by leukaemic cells of unmutated patients. The specific quantification of endogenous LPL protein correlates with mRNA expression levels and mutational IGHV status, suggesting LPL protein as a possible reliable prognostic marker in CLL...
June 28, 2018: British Journal of Haematology
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