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Double-Hit Lymphoma

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https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#1
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28614202/further-exploration-of-the-complexities-of-large-b-cell-lymphomas-with-myc-abnormalities-and-the-importance-of-a-blastoid-morphology
#2
Erika M Moore, Nidhi Aggarwal, Urvashi Surti, Steven H Swerdlow
The 2016 World Health Organization classification recognized "high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements" (double/triple-hit lymphoma [DTHL]) and "high-grade B-cell lymphoma, not otherwise specified," which includes non-DTHL with a "blastoid" or "intermediate" cytology. Although extensively studied, many questions remain, including which cases belong in these categories, which factors mitigate their adverse prognosis, and when to perform fluorescence in situ hybridization studies...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28600333/how-i-treat-double-hit-lymphoma
#3
Jonathan W Friedberg
The 2016 revision of the WHO classification for lymphoma classification has included a new category of lymphoma, separate from diffuse large B-cell lymphoma termed High grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 These lymphomas, which occur in less than 10% of cases of diffuse large B-cell lymphoma, have been referred to as "double hit" lymphomas (or triple hit lymphomas if all three rearrangements are present). It is important to differentiate these lymphomas from the larger group of "double expressor" lymphomas which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, using variable cut-off percentages to define positivity...
June 9, 2017: Blood
https://www.readbyqxmd.com/read/28595732/the-novel-double-hit-t-8-22-q24-q11-myc-igl-and-t-14-15-q32-q24-igh-bcl2a1-in-diffuse-large-b-cell-lymphoma
#4
Takashi Akasaka, Chiyuki Kishimori, Katsuhiro Fukutsuka, Miho Nakagawa, Kayo Takeoka, Masahiko Hayashida, Gen Honjo, Hitoshi Ohno
An 82-year-old woman presented with generalized lymphadenopathy and skin involvement. Lymph node biopsy revealed diffuse large B-cell lymphoma with a high proliferation index. G-banding and fluorescence in situ hybridization showed a hypertetraploid karyotype with two copies of t(8;22)(q24;q11), generating the fusion of MYC and the immunoglobulin λ chain gene (IGL), and two copies of the novel immunoglobulin heavy chain gene (IGH) translocation, t(14;15)(q32;q24). A long-distance inverse polymerase chain reaction (PCR) using nested primer combinations designed for each constant gene of IGH showed that Cγ4 was juxtaposed to the downstream sequence of the BCL2A1 (BCL2-related protein A1) gene through the Sγ4 switch region...
August 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28579851/transformation-of-follicular-lymphoma-to-a-high-grade-b-cell-lymphoma-with-myc-and-bcl2-translocations-and-overlapping-features-of-burkitt-lymphoma-and-acute-lymphoblastic-leukemia-a-case-report-and-literature-review
#5
Alina M Bischin, Russell Dorer, David M Aboulafia
Most commonly, histologic transformation (HT) from follicular lymphoma (FL) manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL) with MYC and B-cell lymphoma protein 2 (BCL2) and/or BCL6 gene rearrangements, also known as "double-hit" or "triple-hit" lymphomas. In the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit...
2017: Clinical Medicine Insights. Blood Disorders
https://www.readbyqxmd.com/read/28512105/double-hit-lymphoma-presenting-as-haemophagocytic-lymphohistiocytosis
#6
Xavier Issac Rivera, Lee J McGhan, Jonathan H Schatz, Soham D Puvvada
No abstract text is available yet for this article.
May 15, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28475457/outcomes-of-patients-with-double-hit-lymphoma-who-achieve-first-complete-remission
#7
Daniel J Landsburg, Marissa K Falkiewicz, Joseph Maly, Kristie A Blum, Christina Howlett, Tatyana Feldman, Anthony R Mato, Brian T Hill, Shaoying Li, L Jeffrey Medeiros, Pallawi Torka, Francisco Hernandez-Ilizaliturri, Nishitha M Reddy, Arun Singavi, Timothy S Fenske, Julio C Chavez, Jason B Kaplan, Amir Behdad, Adam M Petrich, Martin A Bast, Julie M Vose, Adam J Olszewski, Cristiana Costa, Frederick Lansigan, James N Gerson, Stefan K Barta, Oscar Calzada, Jonathon B Cohen, Jennifer K Lue, Jennifer E Amengual, Xavier Rivera, Daniel O Persky, David J Peace, Sunita Nathan, Ryan D Cassaday
Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included...
May 5, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28460620/cx-4945-a-selective-inhibitor-of-casein-kinase-2-synergizes-with-b-cell-receptor-signaling-inhibitors-in-inducing-diffuse-large-b-cell-lymphoma-cell-death
#8
Elisa Mandato, Sara Canovas Nunes, Fortunato Zaffino, Alessandro Casellato, Paolo Macaccaro, Laura Quotti Tubi, Andrea Visentin, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
BACKGROUND: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling thus being a suitable pharmacological target in DLBCL is unknown. OBJECTIVE: To establish if CK2 controls DLBCL cell survival and the BCR signaling; to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents; to survey the changes in signaling molecules downstream BCR upon CK2 inhibition...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28416758/synergistic-interactions-between-plk1-and-hdac-inhibitors-in-non-hodgkin-s-lymphoma-cells-occur-in-vitro-and-in-vivo-and-proceed-through-multiple-mechanisms
#9
Tri Nguyen, Rebecca Parker, Elisa Hawkins, Beata Holkova, Victor Yazbeck, Akhil Kolluri, Maciej Kmieciak, Mohamed Rahmani, Steven Grant
Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo. Exposure of DLBCL cells to very low concentrations of volasertib in combination with belinostat synergistically increased cell death (apoptosis). Similar interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib-resistant cells and primary lymphoma cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398499/outcome-of-elderly-patients-with-diffuse-large-b-cell-lymphoma-treated-with-r-chop-results-from-the-uk-ncri-r-chop14v21-trial-with-combined-analysis-of-molecular-characteristics-with-the-dshnhl-ricover-60-trial
#10
A Kühnl, D Cunningham, N Counsell, E A Hawkes, W Qian, P Smith, N Chadwick, A Lawrie, P Mouncey, A Jack, C Pocock, K M Ardeshna, J Radford, A McMillan, J Davies, D Turner, A Kruger, P Johnson, J Gambell, A Rosenwald, G Ott, H Horn, M Ziepert, M Pfreundschuh, D Linch
BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up...
April 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382141/overexpression-of-myc-and-bcl2-predicts-poor-prognosis-in-patients-with-extranodal-nk-t-cell-lymphoma-nasal-type
#11
Jing-Hua Wang, Xi-Wen Bi, Peng-Fei Li, Zhong-Jun Xia, Hui-Qiang Huang, Wen-Qi Jiang, Yu-Jing Zhang, Liang Wang
Background: Recently double-hit lymphoma or double protein expressor lymphoma has been identified as a distinct group of diffuse large B cell lymphoma with poor prognosis. However, the expression status, clinical and prognostic effect of combined overexpression of MYC and BCL2 in extranodal NK/T-cell lymphoma, nasal type (ENKTL) are not known. Materials and methods: Paraffin-embedded lymphoma samples from 53 patients with newly diagnosed ENKTL were studied using immunohistochemistry for MYC and BCL2, and fluorescent in situ hybridization (FISH) for MYC and BCL2 were done on 5 tissue sections with highest percentages of both MYC and BCL2 positive lymphoma cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28379189/the-role-of-c-myc-in-b-cell-lymphomas-diagnostic-and-molecular-aspects
#12
REVIEW
Lynh Nguyen, Peter Papenhausen, Haipeng Shao
c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes...
April 5, 2017: Genes
https://www.readbyqxmd.com/read/28357165/persistent-afebrile-abdominal-pain-an-unusual-case-of-segmental-colitis-in-an-immunocompromised-host
#13
Ilias P Papakonstantinou, Emmanuel A Andreadis
In this report we describe a case of a 66-year-old woman who presented with right upper quadrant abdominal pain and bloody diarrhea. A workup revealed immunodeficiency, an immunologic profile with low complement levels resembling systemic lupus erythematosus, and a circumferential colonic wall lesion located in the ascending colon. After endoscopy and biopsy, the mass lesion was attributed to "double hit" diffuse large B-cell lymphoma, categorized as high grade large B-cell non-Hodgkin lymphoma according to the most recent revised 2016 World Health Organisation classification and considered to be a rare and highly aggressive tumor...
February 16, 2017: Curēus
https://www.readbyqxmd.com/read/28321092/refractory-double-hit-lymphoma-leukemia-in-childhood-mimicking-b-precursor-acute-lymphoblastic-leukemia-at-initial-presentation
#14
REVIEW
Suguru Uemura, Daiichiro Hasegawa, Takehito Yokoi, Nanako Nino, Teppei Tahara, Akihiro Tamura, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Keiichiro Kawasaki, Nobuyuki Yamamoto, Takeshi Mori, Noriyuki Nishimura, Yoshiyuki Kosaka
A 10-year-old girl was referred to our hospital with left preauricular adenopathy and gingival swelling. She was diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on being positive for expressions of CD10, CD19, TdT and HLA-DR. She showed no CD20 expression at the time of diagnosis. Based on the initial diagnosis of BCP-ALL, induction chemotherapy for BCP-ALL was initiated. However, the blasts did not disappear from her peripheral blood. Bone marrow examination on day 33 identified 81...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28229364/molecular-subtyping-in-diffuse-large-b-cell-lymphoma-closer-to-an-approach-of-precision-therapy
#15
REVIEW
Reem Karmali, Leo I Gordon
It has become clear that there is immense biological heterogeneity in diffuse large B cell lymphoma (DLBCL). Developing technology has allowed better characterization of patient subsets at a molecular level, allowing for a link of phenotype and clinical outcomes to oncogenic mechanisms and biologic signatures. Cell of origin and double hit status are able to identify aggressive subsets, with molecular profiling allowing for a clearer understanding of biologic pathways that contribute to cellular resistance to conventional treatment in these subsets...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28212368/aggressive-b-cell-lymphoma-the-double-hit-and-double-expressor-phenotypes
#16
Sonali M Smith
No abstract text is available yet for this article.
January 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28061782/double-hit-lymphomas-clinical-morphological-immunohistochemical-and-cytogenetic-study-in-a-series-of-brazilian-patients-with-high-grade-non-hodgkin-lymphoma
#17
Cristiano Claudino Oliveira, Helena Maciel-Guerra, Luan Kucko, Eric Jun Hirama, Américo Delgado Brilhante, Francisco Carlos Quevedo, Isabela Werneck da Cunha, Fernando Augusto Soares, Ligia Niero-Melo, Patrícia Pintor Dos Reis, Maria Aparecida Custodio Domingues
BACKGROUND: Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases. METHOD: Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted...
January 7, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28034071/relapsed-or-refractory-double-expressor-and-double-hit-lymphomas-have-inferior-progression-free-survival-after-autologous-stem-cell-transplantation
#18
Alex F Herrera, Matthew Mei, Lawrence Low, Haesook T Kim, Gabriel K Griffin, Joo Y Song, Reid W Merryman, Victoria Bedell, Christine Pak, Heather Sun, Tanya Paris, Tracey Stiller, Jennifer R Brown, Lihua E Budde, Wing C Chan, Robert Chen, Matthew S Davids, Arnold S Freedman, David C Fisher, Eric D Jacobsen, Caron A Jacobson, Ann S LaCasce, Joyce Murata-Collins, Auayporn P Nademanee, Joycelynne M Palmer, German A Pihan, Raju Pillai, Leslie Popplewell, Tanya Siddiqi, Aliyah R Sohani, Jasmine Zain, Steven T Rosen, Larry W Kwak, David M Weinstock, Stephen J Forman, Dennis D Weisenburger, Young Kim, Scott J Rodig, Amrita Krishnan, Philippe Armand
Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled...
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28034063/impact-of-double-hit-and-double-expressor-phenotypes-in-relapsed-aggressive-b-cell-lymphomas-treated-with-autologous-hematopoietic-stem-cell-transplantation
#19
Sonali M Smith
No abstract text is available yet for this article.
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27986884/beyond-rchop-a-blueprint-for-diffuse-large-b-cell-lymphoma-research
#20
REVIEW
Grzegorz S Nowakowski, Kristie A Blum, Brad S Kahl, Jonathan W Friedberg, Lawrence Baizer, Richard F Little, David G Maloney, Laurie H Sehn, Michael E Williams, Wyndham H Wilson, John P Leonard, Sonali M Smith
Diffuse large B cell lymphoma (DLBCL) comprises multiple molecular and biological subtypes, resulting in a broad range of clinical outcomes. With standard chemoimmunotherapy, there remains an unacceptably high treatment failure rate in certain DLBCL subsets: activated B cell (ABC) DLBCL, double-hit lymphoma defined by the dual translocation of MYC and BCL2, dual protein-expressing lymphomas defined by the overexpression of MYC and BCL2, and older patients and those with central nervous system involvement. The main research challenges for DLBCL are to accurately identify molecular subsets and to determine if specific chemotherapy platforms and targeted agents offer differential benefit...
December 2016: Journal of the National Cancer Institute
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