372 research outputs found
Cytogenetic and molecular analysis of the acute monocytic leukemia cell line THP‐1 with an MLLAF9 translocation
Injection safety knowledge and practices among clinical health care workers in Garissa provincial general hospital
Background: The World Health Organization estimates that approximately 16 billion injections are administered in developing countries annually. Injection safety is therefore critical in preventing occupational exposure and infection from blood borne pathogens, hence prevention is a vital part of any comprehensive plan for protecting health workers, patients and maintaining a safe environment.Objective: To determine the knowledge and practice of injection safety among clinical healthcare workers at the Garissa Provincial General Hospital.Design: A cross-sectional descriptive study.Setting: The Garissa provincial General Hospital from September 2011 to July 2012.Results: Injection safety knowledge was high with a score of 12.65 (SD ± 2.3) out of the total of 16 items. Appropriate injection safety practices were reported by most of the respondents. The level of knowledge was not significantly associated with respondents’ demographic characteristics(p>0.05), but was significantly associated with hand washing practice(p<0.05).Inferences were made on an appropriate injection safety practices like non-recapping of needles, hand washing and proper waste management. Drug administration practice varied in the different departments (p=0.043) and recapping of needles was significantly associated with training (p=0.047), designation (p=0.02) and area of deployment (p=0.017).Conclusion: Knowledge on injection safety was high but reported and observed practices were below the set standard. Risky practices such as recapping used syringes, re-use of disposable syringes and overfilling of sharp boxes were observed. There was insufficient provision of injection safety equipment, Poor waste handling and inadequate personal protective gear. Over prescription of unnecessary injections was widespread
Cytogenetic and molecular analysis of the acute monocytic leukemia cell line THP-1 with an MLL-AF9 translocation
Cell lines derived from patients with leukemia are used in many molecular biology studies. Here we report the cytogenetic analysis of the THP-1 cell line using G-banding, fluorescence in situ hybridization (FISH), and spectral karyotyping (SKY), and the molecular characterization of the MLL-AF9 rearrangement by RT-PCR. The THP-1 cell line was established from the peripheral blood of a 1-year-old boy with acute monocytic leukemia (AML-M5). THP-1 is near-diploid and consists of two related subclones with a number of aberrations, including the t(9;11), associated with AML M5. The use of FISH allowed us to identify and characterize otherwise hidden cytogenetic rearrangements, which include duplication of the 3' portion of MLL in the derivative 9 chromosome and a deletion of the 5' portion of the AF9 gene involved in the translocation. In addition to confirming the FISH results, SKY allowed for a more precise characterization of the karyotype of THP-1 and allowed us to identify other abnormalities in this cell line, including der(1)t(1;12), der(20)t(1;20), deletions 6p, 12p, and 17p, trisomy 8, and monosomy 10. Sequencing of the RT-PCR product showed a direct in-frame fusion product on the derivative chromosome 11 between exon 6 (exon 9) of MLL and exon 5 of AF9, which is most commonly involved in MLL-AF9 translocations. This study demonstrates that combining different techniques to achieve a more precise characterization of the THP-1 cell line provides important information that will be valuable for understanding the critical events required for leukemogenesis
A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15
The mixed lineage leukemia gene (MLL, also known as HRX, ALL-1 and Htrx) located at 11q23 is involved in translocations with over 40 different chromosomal bands in a variety of leukemia subtypes. Here we report our analysis of a rare but recurring translocation, t(11;15)(q23;q14). This translocation has been described in a small subset of cases with both acute myeloblastic leukemia and ALL. Recent studies have shown that MLL is fused to AF15q14 in the t(11;15). Here we analyse a sample from another patient with this translocation and confirm the presence of an MLL-AF15q14 fusion. However, we have also identified and cloned another fusion transcript from the same patient sample. In this fusion transcript, MLL is fused to a novel gene, MLL partner containing FYVE domain (MPFYVE). Both MLL-AF15q14 and MLL-MPFYVE are in-frame fusion transcripts with the potential to code for novel fusion proteins. MPFYVE is also located on chromosome 15, approximately 170 kb telomeric to AF15q14. MPFYVE contains a highly conserved motif, the FYVE domain which, in other proteins, has been shown to bind to phosphotidyl-inositol-3 phosphate (PtdIns(3)P). The MLL-MPFYVE fusion may be functionally important in the leukemia process in at least some patients containing this translocation
SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia
3 Tables. 7 Figures. The online version of this article contains a data supplement.Acute myeloid leukemias (AMLs) result from multiple genetic alterations in hematopoietic stem cells. We describe a novel t(12;18)(p13;q12) involving ETV6 in a patient with AML. The translocation resulted in overexpression of SETBP1 (18q12), located close to the breakpoint. Overexpression of SETBP1 through retroviral insertion has been reported to confer growth advantage in hematopoietic progenitor cells. We show that SETBP1 overexpression protects SET from protease cleavage, increasing the amount of full-length SET protein and leading to the formation of a SETBP1–SET-PP2A complex that results in PP2A inhibition, promoting proliferation of the leukemic cells. The prevalence of SETBP1 overexpression in AML at diagnosis (n = 192) was 27.6% and was associated with unfavorable cytogenetic prognostic group, monosomy 7, and EVI1 overexpression (P < .01). Patients with SETBP1 overexpression had a significantly shorter overall survival, and the prognosis impact was remarkably poor in patients older than 60 years in both overall survival (P = .015) and event-free survival (P = .015). In summary, our data show a novel leukemogenic mechanism through SETBP1 overexpression; moreover, multivariate analysis confirms the negative prognostic impact of SETBP1 overexpression in AML, especially in elderly patients, where it could be used as a predictive factor in any future clinical trials with PP2A activators.This work was supported by the Ministerio de Educación y Ciencia, Ministerio de Ciencia e Innovación (PI081687, M.D.O.; and SAF2007-61827, C.B.), Departamento de Salud del Gobierno de Navarra (14/2008), ISCIII-RTICC (RD06/0020/0078), and Fundación para la Investigación Médica Aplicada y UTE (Spain).Elizabeth Guruceaga, of the Unit of Proteomics,Genomics and Bioinformatics of Center for Applied Medical Research, for the bioinformatics analysis, and Enrique Andreu for useful discussionPeer reviewe
Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13)
The ETV6 gene (first identified as TEL) is a frequent target of chromosomal translocations in both myeloid and lymphoid leukemias. At present, more than 40 distinct translocations have been cytogenetically described, of which 13 have now also been characterized at the molecular level. These studies revealed the generation of in-frame fusion genes between different domains of ETV6 and partner genes encoding either kinases or transcription factors. However, in a number of cases-including a t(6;12)(q23;p13), the recurrent t(5;12)(q31;p13), and some cases of the t(4;12)(q11-q12;p13) described in this work-functionally significant fusions could not be identified, raising the question as to what leukemogenic mechanism is implicated in these cases. To investigate this, we have evaluated the genomic regions at 4q11-q12 and 5q31, telomeric to the breakpoints of the t(4;12)(q11-q12;p13) and t(5;12)(q31;p13). The homeobox gene GSH2 at 4q11-q12 and the IL-3/CSF2 locus at 5q31 were found to be located close to the respective breakpoints. In addition, GSH2 and IL-3 were found to be ectopically expressed in the leukemic cells, suggesting that expression of GSH2 and IL-3 was deregulated by the translocation. Our results indicate that, besides the generation of fusion transcripts, deregulation of the expression of oncogenes could be a variant leukemogenic mechanism for translocations involving the 5' end of ETV6, especially for those translocations lacking functionally significant fusion transcripts
A variant t(14;17) in acute promyelocytic leukemia. Positive response to retinoic acid treatment
We present a case of acute promyelocytic leukemia (APL) carrying an atypical translocation involving chromosomes 14 and 17. This translocation could be considered a variant of the APL-specific t(15;17). Positive response to retinoic acid treatment suggests molecular rearrangement of retinoic acid receptor alpha
Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas
AIMS:
The aim of this work is the study of the prognostic significance of the chromosomal aberrations described in a series of invasive ductal breast carcinomas.
METHODS AND RESULTS:
We analysed by comparative genomic hybridization a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas. Aberrations showed a frequency similar to previous studies using frozen tumours. Interestingly, we identified gains involving 6q16-q24 more frequently than in other series. We analysed the association among the chromosomal imbalances, 11 histopathological factors, relapse rate and overall survival of patients. Associations showed 16q losses as a potential marker of good prognosis, as they were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063; P=0.066). Within the good prognosis group of lymph node-negative patients, 17q and 20q gains identify a subgroup with increased relapse rate (P=0.039).
CONCLUSIONS:
Chromosomal imbalances, together with histopathological factors, may help to predict outcome in breast cancer patients
A recurrent translocation, t(3;11)(q21;q13), found in two distinct cases of acute myeloid leukemia
We report two cases of acute myeloid leukemia (M1 and M5B subtypes) with a similar translocation, t(3;11)(q21;q13). We discuss the involvement of these breakpoints in acute leukemia and their putative clinical implications
Harnessing Technology to Enable the Flow of Professional Capital:Exploring Experiences of Professional Learning in Rural Scotland
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