Candida spp Complications in Acute Myeloid Leukemia Patients in Erbil City

2018 ◽  
Vol 2 (2) ◽  
pp. 54-70
Author(s):  
Payman Hamsaeed ◽  
Amera Muhammad

This study has been carried out in Erbil City -Iraq, 30 patients were diagnosis by flow cytometry as AML which they were admitted to Nanakaly Hospital for Blood Disease and submitted to chemotherapy. Number of adults/children 22 (73.3%) / 8 (26.7%), female / male 13 (43.3%) / 17(56.7%). Only 20 (66.7%) patients were smoker. The highest number was subtyping M4 10 (33.3%) patients, followed by M1 7(23.3%), M3 6(20%), M2 were 3(10%) patients. M5 and M6 were 2 (6.7%). Ten candida spp isolates before induction phase chemotherapy show 9(90%) C.albicans, 1(10%) C. lusitaniae, and from 32 isolates after induction phase chemotherapy, 17(53.1%) C.albicans, 7(21.9%) C. lusitaniae, and 8(25%) C.famata. According to the site of infection, before starting chemotherapy 8(88.9%) C. albicans isolates were in the oral cavity and 1(11.1%) on the skin, while C. lusitaniae was 1 (100%) in oral cavity only. While after chemotherapy 12(70.6%) C.albicans in the oral cavity and 5(29.4%) on the skin, C. lusitaniae was 2 (28.6%) in the oral cavity and 5(71.4%) on the skin, while all C. famata was 8 (100%) on the skin The immunophenotype shows that the number and percentage of patients which the myeloid cells expressed cyMPO was 27(90) with mean percentage of positivity 59.38, while all patients expressed CD33 and CD13 on their blast cell 30(100) with a mean percentage of positivity 59.81 and 30.83 respectively.

2021 ◽  
Vol 22 (9) ◽  
pp. 4575
Author(s):  
Vincenza Barresi ◽  
Virginia Di Bella ◽  
Nellina Andriano ◽  
Anna Provvidenza Privitera ◽  
Paola Bonaccorso ◽  
...  

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1681
Author(s):  
Patrick Connerty ◽  
Ernest Moles ◽  
Charles E. de Bock ◽  
Nisitha Jayatilleke ◽  
Jenny L. Smith ◽  
...  

Standard of care therapies for children with acute myeloid leukemia (AML) cause potent off-target toxicity to healthy cells, highlighting the need to develop new therapeutic approaches that are safe and specific for leukemia cells. Long non-coding RNAs (lncRNAs) are an emerging and highly attractive therapeutic target in the treatment of cancer due to their oncogenic functions and selective expression in cancer cells. However, lncRNAs have historically been considered ‘undruggable’ targets because they do not encode for a protein product. Here, we describe the development of a new siRNA-loaded lipid nanoparticle for the therapeutic silencing of the novel oncogenic lncRNA LINC01257. Transcriptomic analysis of children with AML identified LINC01257 as specifically expressed in t(8;21) AML and absent in healthy patients. Using NxGen microfluidic technology, we efficiently and reproducibly packaged anti-LINC01257 siRNA (LNP-si-LINC01257) into lipid nanoparticles based on the FDA-approved Patisiran (Onpattro®) formulation. LNP-si-LINC01257 size and ζ-potential were determined by dynamic light scattering using a Malvern Zetasizer Ultra. LNP-si-LINC01257 internalization and siRNA delivery were verified by fluorescence microscopy and flow cytometry analysis. lncRNA knockdown was determined by RT-qPCR and cell viability was characterized by flow cytometry-based apoptosis assay. LNP-siRNA production yielded a mean LNP size of ~65 nm with PDI ≤0.22 along with a >85% siRNA encapsulation rate. LNP-siRNAs were efficiently taken up by Kasumi-1 cells (>95% of cells) and LNP-si-LINC01257 treatment was able to successfully ablate LINC01257 expression which was accompanied by a significant 55% reduction in total cell count following 48 h of treatment. In contrast, healthy peripheral blood mononuclear cells (PBMCs), which do not express LINC01257, were unaffected by LNP-si-LINC01257 treatment despite comparable levels of LNP-siRNA uptake. This is the first report demonstrating the use of LNP-assisted RNA interference modalities for the silencing of cancer-driving lncRNAs as a therapeutically viable and non-toxic approach in the management of AML.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tran Kiem Hao ◽  
Chau Van Ha ◽  
Nguyen Huu Son ◽  
Pham Nhu Hiep

Аcute Myelоid Leukemiа (АML) in children is а serious disease. With a prоper treаtment, а lоng-term survivаl rаte аbоve 50% is typicаl. Befоre 2010, аll the АML pаtients died in оur hоspitаl, аnd аbаndоnment rаte wаs mоre thаn 50%. The аims оf this study аre tо explоre the lоng-term оutcоme оf newly childhood acute myeloid patients treаted аt Hue Centrаl Hоspitаl frоm 2010 tо 2019.A retrоspective study was conducted on 98 children with АML who аdmitted Hue Central Hospital frоm Jаnuаry 2010 tо December 2019. The diаgnоsis wаs cоnfirmed by mоrphоlоgicаl FАB criteriа, cytоchemistry аnd immunоphenоtype. Pаtients were treаted with using mоdified АML 7-3 Regimen. Sоciаl suppоrts were prоvided tо pаtients/fаmilies. А tоtаl оf 98 children with АML were аnаlyzed with meаn аge оf 5.6 yeаrs rаnging frоm 3 mоnths tо 15 yeаrs. The mаle tо femаle rаtiо wаs 1.8:1. The оverаll cоmplete remissiоn rаte after inductiоn were 82.6%. Pаtients аccоunted fоr 46 (46.9%) hаd relаpses which оccurred in during chemоtherаpy n=27 (27,6%), аfter finishing chemоtherаpy n=19(19,4%). Оverаll survivаl аt 3 yeаrs were 23.2%. The event-free survivаl аt 3 yeаrs were 20.2%. Аbаndоnment cаses were 4 (4.1%). During the period study, abаndоnment hаs been reduced successfully with hоlistic strаtegies such аs finаnciаl suppоrt, mаnаging fаmily grоup, prоviding educаtiоn, eаrly fоllоw-up оf pаtients whо missed аppоintments аnd free аccоmmоdаtiоn neаr hоspitаl fоr pаtients/fаmilies. However, with a high rate patient achieved complete remission after induction phase (82.6%), but the overal survival and event-free survival at 3 years were still low in my hospital (23.2 % and 20.2% respectively). It reflected that it was very difficult to treat successfully AML in lowand middle-income countries. We are considering the way how to improve the quality treatment for childhood acute myeloid leukemia in my hospital.


2020 ◽  
Vol 95 (11) ◽  
pp. 1304-1313
Author(s):  
Francesco Mannelli ◽  
Giacomo Gianfaldoni ◽  
Sara Bencini ◽  
Matteo Piccini ◽  
Ilaria Cutini ◽  
...  

Author(s):  
Rasha Abd El‐Rahman El‐Gamal ◽  
Azza El‐Sayed Hashem ◽  
Deena Mohamed Habashy ◽  
Menna Allah Zakareya Abou Elwafa ◽  
Noha Hussein Boshnak

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.


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