PMID- 25563586
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20220321
IS  - 2211-3436 (Electronic)
IS  - 2211-3428 (Linking)
VI  - 38
IP  - 2
DP  - 2015 Apr
TI  - Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis.
PG  - 93-109
LID - 10.1007/s13402-014-0215-3 [doi]
AB  - BACKGROUNDS: Chronic lymphocytic leukemia (CLL) is the most common type of 
      leukemia in adults and is characterized by a clonal accumulation of mature 
      apoptosis-resistant neoplastic cells. It is also a heterogeneous disease with a 
      variable clinical outcome. Here, we present a review of currently known 
      (epi)genetic alterations that are related to the etiology, progression and 
      chemo-refractoriness of CLL. Relevant literature was identified through a PubMed 
      search (1994-2014) of English-language papers using the terms CLL, signaling 
      pathway, cytogenetic abnormality, somatic mutation, epigenetic alteration and 
      micro-RNA. RESULTS: CLL is characterized by the presence of gross chromosomal 
      abnormalities, epigenetic alterations, micro-RNA expression alterations, 
      immunoglobulin heavy chain gene mutations and other genetic lesions. The 
      expression of unmutated immunoglobulin heavy chain variable region (IGHV) genes, 
      ZAP-70 and CD38 proteins, the occurrence of chromosomal abnormalities such as 17p 
      and 11q deletions and mutations of the NOTCH1, SF3B1 and BIRC3 genes have been 
      associated with a poor prognosis. In addition, mutations in tumor suppressor 
      genes, such as TP53 and ATM, have been associated with refractoriness to 
      conventional chemotherapeutic agents. Micro-RNA expression alterations and 
      aberrant methylation patterns in genes that are specifically deregulated in CLL, 
      including the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and linked 
      to distinct clinical parameters. CONCLUSIONS: Specific chromosomal abnormalities 
      and gene mutations may serve as diagnostic and prognostic indicators for disease 
      progression and survival. The identification of these anomalies by 
      state-of-the-art molecular (cyto)genetic techniques such as fluorescence in situ 
      hybridization (FISH), comparative genomic hybridization (CGH), single nucleotide 
      polymorphism (SNP) microarray-based genomic profiling and next-generation 
      sequencing (NGS) can be of paramount help for the clinical management of these 
      patients, including optimal treatment design. The efficacy of novel therapeutics 
      should to be tested according to the presence of these molecular lesions in CLL 
      patients.
FAU - Shahjahani, Mohammad
AU  - Shahjahani M
AD  - Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat 
      Modares University, Tehran, Iran.
FAU - Mohammadiasl, Javad
AU  - Mohammadiasl J
FAU - Noroozi, Fatemeh
AU  - Noroozi F
FAU - Seghatoleslami, Mohammad
AU  - Seghatoleslami M
FAU - Shahrabi, Saeid
AU  - Shahrabi S
FAU - Saba, Fakhredin
AU  - Saba F
FAU - Saki, Najmaldin
AU  - Saki N
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20150107
PL  - Netherlands
TA  - Cell Oncol (Dordr)
JT  - Cellular oncology (Dordrecht)
JID - 101552938
SB  - IM
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*genetics/mortality
MH  - Prognosis
EDAT- 2015/01/08 06:00
MHDA- 2016/02/05 06:00
CRDT- 2015/01/08 06:00
PHST- 2014/12/23 00:00 [accepted]
PHST- 2015/01/08 06:00 [entrez]
PHST- 2015/01/08 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
AID - 10.1007/s13402-014-0215-3 [doi]
PST - ppublish
SO  - Cell Oncol (Dordr). 2015 Apr;38(2):93-109. doi: 10.1007/s13402-014-0215-3. Epub 
      2015 Jan 7.