PMID- 26834954
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160202
LR  - 20200930
IS  - 2040-6207 (Print)
IS  - 2040-6215 (Electronic)
IS  - 2040-6207 (Linking)
VI  - 7
IP  - 1
DP  - 2016 Feb
TI  - Current challenges and novel treatment strategies in double hit lymphomas.
PG  - 52-64
LID - 10.1177/2040620715608091 [doi]
AB  - High-grade B-cell lymphomas with recurrent chromosomal break points have been 
      termed 'double hit lymphoma' (DHL). The most commonly seen DHL is diffuse large 
      B-cell lymphoma (DLBCL) with t(14;18) and t(8;14) or t(8;22) resulting in 
      overexpression of BCL2 and MYC, respectively. The increased proliferation due to 
      MYC overexpression, without the ability for an apoptotic brake as a result of 
      BCL2 overexpression, results in 'the perfect storm of oncogenesis'. Thus this 
      disease presents a number of diagnostic and therapeutic challenges for the 
      hematologist. The first and foremost challenge is to recognize the DHL. As 
      different morphological entities can be affected it is incumbent on pathologists 
      and clinicians to maintain a high index of suspicion especially in disease that 
      appears unusually aggressive or refractory to therapy. Diagnosis by fluorescence 
      in situ hybridization (FISH) is a sensitive and specific method for detection of 
      the disease but is time-consuming and expensive. While detection by 
      immunohistochemistry (IHC) is sensitive and correlates with survival, 
      standardized methods for this are not widely agreed upon. The second and equally 
      important challenge in DHL is optimizing clinical outcome in a group of patients 
      for whom the prognosis is widely regarded as poor. While improvements have been 
      achieved by dose escalating standard chemotherapeutic regimens, many patients 
      continue to do badly. Furthermore as a disease of aging many patients are 
      unsuitable for dose-intensive chemotherapy regimens. There are now multiple novel 
      targeted agents in various stages of clinical development that offer hope for 
      better outcomes without undue toxicity. Among the most exciting of these 
      developments include specific inhibitors of both BCL2 and MYC.
FAU - Anderson, Mary Ann
AU  - Anderson MA
AD  - The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade 
      Parkville, Victoria 3052, Australia.
FAU - Tsui, Alpha
AU  - Tsui A
AD  - Department of Pathology, Royal Melbourne Hospital, Parkville, Australia.
FAU - Wall, Meaghan
AU  - Wall M
AD  - Victorian Cancer Cytogenetics Service, St Vincent's Hospital, Fitzroy, Australia.
FAU - Huang, David C S
AU  - Huang DC
AD  - Departments of Medical Biology and Medicine, Faculty of Medicine, University of 
      Melbourne, Parkville, Australia.
FAU - Roberts, Andrew W
AU  - Roberts AW
AD  - Department of Clinical Hematology and Bone Marrow Transplant, Royal Melbourne 
      Hospital, Parkville, Australia.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Ther Adv Hematol
JT  - Therapeutic advances in hematology
JID - 101549589
PMC - PMC4713886
OTO - NOTNLM
OT  - BCL-2
OT  - MYC
OT  - diffuse large B-cell lymphoma
OT  - double hit lymphoma
COIS- Conflict of interest statement: The author(s) declared the following potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: Research funding from AbbVie and Genentech; Employee 
      of Walter and Eliza Hall Institute of Medical Research which receives milestone 
      payments related to venetoclax.
EDAT- 2016/02/03 06:00
MHDA- 2016/02/03 06:01
PMCR- 2016/02/01
CRDT- 2016/02/03 06:00
PHST- 2016/02/03 06:00 [entrez]
PHST- 2016/02/03 06:00 [pubmed]
PHST- 2016/02/03 06:01 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - 10.1177_2040620715608091 [pii]
AID - 10.1177/2040620715608091 [doi]
PST - ppublish
SO  - Ther Adv Hematol. 2016 Feb;7(1):52-64. doi: 10.1177/2040620715608091.