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Fusion genes in malignant neoplastic disorders of haematopoietic system

Saleem M, Yusoff NM

Hematology, 2016 Oct;21(9):501-12.
PMID: 26871368 DOI: 10.1080/10245332.2015.1106816

OBJECTIVES: The new World Health Organization's (WHO) classification of haematopoietic and lymphoid tissue neoplasms incorporating the recurrent fusion genes as the defining criteria for different haematopoietic malignant phenotypes is reviewed. The recurrent fusion genes incorporated in the new WHO's classification and other chromosomal rearrangements of haematopoietic and lymphoid tissue neoplasms are reviewed.
METHODOLOGY: Cytokines and transcription factors in haematopoiesis and leukaemic mechanisms are described. Genetic features and clinical implications due to the encoded chimeric neoproteins causing malignant haematopoietic disorders are reviewed.
RESULTS AND DISCUSSION: Multiple translocation partner genes are well known for leukaemia such as MYC, MLL, RARA, ALK, and RUNX1. With the advent of more sophisticated diagnostic tools and bioinformatics algorithms, an exponential growth in fusion genes discoveries is likely to increase.
CONCLUSION: Demonstration of fusion genes and their specific translocation breakpoints in malignant haematological disorders are crucial for understanding the molecular pathogenesis and clinical phenotype of cancer, determining prognostic indexes and therapeutic responses, and monitoring residual disease and relapse status.

Matched MeSH terms: Gene Fusion*
Low prevalence of the BCR-ABL1 fusion gene in a normal population in southern Sarawak

Kuan JW, Su AT, Tay SP, Fong IL, Kubota S, Su'ut L, et al.

Int J Hematol, 2020 Feb;111(2):217-224.
PMID: 31707540 DOI: 10.1007/s12185-019-02768-x

The BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Its expression level in CML patients is monitored by a real-time quantitative polymerase chain reaction defined by the International Scale (qPCRIS). BCR-ABL1 has also been found in asymptomatic normal individuals using a non-qPCRIS method. In the present study, we examined the prevalence of BCR-ABL1 in a normal population in southern Sarawak by performing qPCRIS for BCR-ABL1 with ABL1 as an internal control on total white blood cells, using an unbiased sampling method. While 146 of 190 (76.8%) or 102 of 190 (53.7%) samples showed sufficient amplification of the ABL1 gene at > 20,000 or > 100,000 copy numbers, respectively, in qPCRIS, one of the 190 samples showed amplification of BCR-ABL1 with positive qPCRIS of 0.0023% and 0.0032% in two independent experiments, the sequence of which was the BCR-ABL1 e13a2 transcript. Thus, we herein demonstrated that the BCR-ABL1 fusion gene is expected to be present in approximately 0.5-1% of normal individuals in southern Sarawak.

Matched MeSH terms: Gene Fusion*
Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases

Zakaria Z, Othman N, Ismail A, Kamaluddin NR, Esa E, Abdul Rahman EJ, et al.

Asian Pac J Cancer Prev, 2017 04 01;18(4):1169-1175.
PMID: 28548470

Background: ETV6/RUNX1 gene fusion is the most frequently seen chromosomal abnormality in childhood acute
lymphobastic leukamia (ALL). However, additional genetic changes are known to be required for the development of
this type of leukaemia. Therefore, we here aimed to assess the somatic mutational profile of four ALL cases carrying the
ETV6/RUNX1 fusion gene using whole-exome sequencing. Methods: DNA was isolated from bone marrow samples
using a QIAmp DNA Blood Mini kit and subsequently sequenced using the Illumina MiSeq system. Results: We
identified 12,960 to17,601 mutations in each sample, with a total of 16,466 somatic mutations in total. Some 15,533
variants were single nucleotide polymorphisms (SNPs), 129 were substitutions, 415 were insertions and 389 were
deletions. When taking into account the coding region and protein impact, 1,875 variants were synonymous and 1,956
were non-synonymous SNPs. Among non-synonymous SNPs, 1,862 were missense, 13 nonsense, 35 frameshifts, 11
nonstop, 3 misstart, 15 splices disrupt and 17 in-frame indels. A total of 86 variants were located in leukaemia-related
genes of which 32 variants were located in the coding regions of GLI2, SP140, GATA2, SMAD5, KMT2C, CDH17,
CDX2, FLT3, PML and MOV10L1. Conclusions: Detection and identification of secondary genetic alterations are
important in identifying new therapeutic targets and developing rationally designed treatment regimens with less
toxicity in ALL patients.

Matched MeSH terms: Gene Fusion
Fulltext Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients

Akhter A, Mughal MK, Elyamany G, Sinclair G, Azma RZ, Masir N, et al.

Diagn Pathol, 2016 Sep 15;11(1):89.
PMID: 27632978 DOI: 10.1186/s13000-016-0541-z

The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL.

Matched MeSH terms: Gene Fusion*
Salmonella enterica serovar Typhi cutF is upregulated during environmental stress

Lau KL, Ong EB, Zainudin ZF, Samian MR, Ismail A, Najimudin N

J Gen Appl Microbiol, 2013;59(3):239-44.
PMID: 23863294
Matched MeSH terms: Artificial Gene Fusion
Fulltext A P. falciparum NF54 Reporter Line Expressing mCherry-Luciferase in Gametocytes, Sporozoites, and Liver-Stages

Marin-Mogollon C, Salman AM, Koolen KMJ, Bolscher JM, van Pul FJA, Miyazaki S, et al.

Front Cell Infect Microbiol, 2019;9:96.
PMID: 31058097 DOI: 10.3389/fcimb.2019.00096

Transgenic malaria parasites expressing fluorescent and bioluminescent proteins are valuable tools to interrogate malaria-parasite biology and to evaluate drugs and vaccines. Using CRISPR/Cas9 methodology a transgenic Plasmodium falciparum (Pf) NF54 line was generated that expresses a fusion of mCherry and luciferase genes under the control of the Pf etramp10.3 gene promoter (line mCherry-luc@etramp10.3). Pf etramp10.3 is related to rodent Plasmodium uis4 and the uis4 promoter has been used to drive high transgene expression in rodent parasite sporozoites and liver-stages. We examined transgene expression throughout the complete life cycle and compared this expression to transgenic lines expressing mCherry-luciferase and GFP-luciferase under control of the constitutive gapdh and eef1a promoters. The mCherry-luc@etramp10.3 parasites express mCherry in gametocytes, sporozoites, and liver-stages. While no mCherry signal was detected in asexual blood-stage parasites above background levels, luciferase expression was detected in asexual blood-stages, as well as in gametocytes, sporozoites and liver-stages, with the highest levels of reporter expression detected in stage III-V gametocytes and in sporozoites. The expression of mCherry and luciferase in gametocytes and sporozoites makes this transgenic parasite line suitable to use in in vitro assays that examine the effect of transmission blocking inhibitors and to analyse gametocyte and sporozoite biology.

Matched MeSH terms: Artificial Gene Fusion
Construction of PHB and PHBV multiple-gene vectors driven by an oil palm leaf-specific promoter

Masani MY, Parveez GK, Izawati AM, Lan CP, Siti Nor Akmar A

Plasmid, 2009 Nov;62(3):191-200.
PMID: 19699761 DOI: 10.1016/j.plasmid.2009.08.002

One of the targets in oil palm genetic engineering programme is the production of polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-valerate (PHBV) in the oil palm leaf tissues. Production of PHB requires the use of phbA (beta-ketothiolase type A), phbB (acetoacetyl-CoA reductase) and phbC (PHB synthase) genes of Ralstonia eutropha, whereas bktB (beta-ketothiolase type B), phbB, phbC genes of R. eutropha and tdcB (threonine dehydratase) gene of Escherichia coli were used for PHBV production. Each of these genes was fused with a transit peptide (Tp) of oil palm acyl-carrier-protein (ACP) gene, driven by an oil palm leaf-specific promoter (LSP1) to genetically engineer the PHB/PHBV pathway to the plastids of the leaf tissues. In total, four transformation vectors, designated pLSP15 (PHB) and pLSP20 (PHBV), and pLSP13 (PHB) and pLSP23 (PHBV), were constructed for transformation in Arabidopsis thaliana and oil palm, respectively. The phosphinothricin acetyltransferase gene (bar) driven by CaMV35S promoter in pLSP15 and pLSP20, and ubiquitin promoter in pLSP13 and pLSP23 were used as the plant selectable markers. Matrix attachment region of tobacco (RB7MAR) was also included in the vectors to stabilize the transgene expression and to minimize silencing due to positional effect. Restriction digestion, PCR amplification and/or sequencing were carried out to ensure sequence integrity and orientation.

Matched MeSH terms: Artificial Gene Fusion