scholarly journals ERG11 Gene Mutations and MDR1 Upregulation Confer Pan-Azole Resistance in Candida tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia Patient on Posaconazole Prophylaxis

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Liangshun You ◽  
Wenbin Qian ◽  
Qing Yang ◽  
Liping Mao ◽  
Li Zhu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Candida Tropicalis ◽  
Rare Case ◽  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
Efflux Pumps ◽  
Resistance Mechanisms ◽  
Azole Resistance ◽  
Content Type ◽  
Leukemia Patient

ABSTRACT In this study, we present a rare case of fatal breakthrough Candida tropicalis infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole resistance mechanisms in Candida tropicalis.

scholarly journals Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates

2016 ◽  
Vol 60 (6) ◽  
pp. 3653-3661 ◽  
Author(s):  
Min Ji Choi ◽  
Eun Jeong Won ◽  
Jong Hee Shin ◽  
Soo Hyun Kim ◽  
Wee-Gyo Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
Clinical Features ◽  
Candida Tropicalis ◽  
Resistance Mechanisms ◽  
Therapeutic Failure ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Amino Acid Substitutions ◽  
Content Type ◽  
Expression Levels

We investigated the azole resistance mechanisms and clinical features of fluconazole-nonsusceptible (FNS) isolates ofCandida tropicalisrecovered from Korean surveillance cultures in comparison with fluconazole-less-susceptible (FLS) isolates. Thirty-five clinical isolates ofC. tropicalis, comprising 9 FNS (fluconazole MIC, 4 to 64 μg/ml), 12 FLS (MIC, 1 to 2 μg/ml), and 14 control (MIC, 0.125 to 0.5 μg/ml) isolates, were assessed.CDR1,MDR1, andERG11expression was quantified, and theERG11andUPC2genes were sequenced. Clinical features of 16 patients with FNS or FLS bloodstream isolates were analyzed. Both FNS and FLS isolates had >10-fold higher mean expression levels ofCDR1,MDR1, andERG11genes than control isolates (Pvalues of <0.02 for all). When FNS and FLS isolates were compared, FNS isolates had 3.4-fold higher meanERG11expression levels than FLS isolates (P= 0.004), but there were no differences in those ofCDR1orMDR1. Of all 35 isolates, 4 (2 FNS and 2 FLS) and 28 (8 FNS, 11 FLS, and 9 control) isolates exhibited amino acid substitutions in Erg11p and Upc2p, respectively. Both FNS and FLS bloodstream isolates were associated with azole therapeutic failure (3/4 versus 4/7) or uncleared fungemia (4/6 versus 4/10), but FNS isolates were identified more frequently from patients with previous azole exposure (6/6 versus 3/10;P= 0.011) and immunosuppression (6/6 versus 3/10;P= 0.011). These results reveal that the majority of FNSC. tropicalisisolates show overexpression ofCDR1,MDR1, andERG11genes, and fungemia develops after azole exposure in patients with immunosuppression.

scholarly journals Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis

2012 ◽  
Vol 57 (1) ◽  
pp. 614-617 ◽  
Author(s):  
Rasmus Hare Jensen ◽  
Helle Krogh Johansen ◽  
Maiken Cavling Arendrup
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Amino Acid ◽  
Candida Tropicalis ◽  
Lymphoblastic Leukemia ◽  
Amino Acid Substitutions ◽  
Homozygous Mutation ◽  
Content Type ◽  
Drug Classes ◽  
Stepwise Development ◽  
Echinocandin Resistance

ABSTRACTThreeCandida tropicalisisolates were obtained from a patient with acute lymphoblastic leukemia. The first isolate was susceptible to all drug classes, while isolates 2 and 3, obtained after 8 and 8.5 weeks of caspofungin treatment, respectively, were resistant to the three echinocandins. Multilocus sequence genotyping suggested a clonal relation among all isolates.FKS1sequencing revealed a stepwise development of a heterozygous and finally a homozygous mutation, leading to S80S/P and S80P amino acid substitutions.

scholarly journals P190BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature

2021 ◽  
pp. 1040-1050
Author(s):  
Samah Kohla ◽  
Sarah EL Kourashy ◽  
Zafar Nawaz ◽  
Reda Youssef ◽  
Ahmad Al-Sabbagh ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Rare Case ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Cytogenetic Abnormality ◽  
Rare Case Report ◽  
Philadelphia Chromosome Positive

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 <i>BCR-ABL1</i>) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

scholarly journals Esophageal Erosion as a Possible Bacterial Entry Site in an Acute Lymphoblastic Leukemia Patient with Sepsis

2003 ◽  
Vol 77 (4) ◽  
pp. 395-398 ◽  
Author(s):  
Satoshi Ikegaya ◽  
Hironobu Naiki ◽  
Akira Yoshida ◽  
Takanori Ueda ◽  
Hiromichi Iwasaki
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Entry Site ◽  
Leukemia Patient ◽  
Esophageal Erosion

scholarly journals Magnitude of Voriconazole Resistance in Clinical and Environmental Isolates of Aspergillus flavus and Investigation into the Role of Multidrug Efflux Pumps

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Raees A. Paul ◽  
Shivaprakash M. Rudramurthy ◽  
Manpreet Dhaliwal ◽  
Pankaj Singh ◽  
Anup K. Ghosh ◽  
...  
Keyword(s):  
Aspergillus Flavus ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Azole Resistance ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Environmental Isolates ◽  
Content Type ◽  
Multidrug Efflux Pumps

ABSTRACT The magnitude of azole resistance in Aspergillus flavus and its underlying mechanism is obscure. We evaluated the frequency of azole resistance in a collection of clinical (n = 121) and environmental isolates (n = 68) of A. flavus by the broth microdilution method. Six (5%) clinical isolates displayed voriconazole MIC greater than the epidemiological cutoff value. Two of these isolates with non-wild-type MIC were isolated from same patient and were genetically distinct, which was confirmed by amplified fragment length polymorphism analysis. Mutations associated with azole resistance were not present in the lanosterol 14-α demethylase coding genes (cyp51A, cyp51B, and cyp51C). Basal and voriconazole-induced expression of cyp51A homologs and various efflux pump genes was analyzed in three each of non-wild-type and wild-type isolates. All of the efflux pump genes screened showed low basal expression irrespective of the azole susceptibility of the isolate. However, the non-wild-type isolates demonstrated heterogeneous overexpression of many efflux pumps and the target enzyme coding genes in response to induction with voriconazole (1 μg/ml). The most distinctive observation was approximately 8- to 9-fold voriconazole-induced overexpression of an ortholog of the Candida albicans ATP binding cassette (ABC) multidrug efflux transporter, Cdr1, in two non-wild-type isolates compared to those in the reference strain A. flavus ATCC 204304 and other wild-type strains. Although the dominant marker of azole resistance in A. flavus is still elusive, the current study proposes the possible role of multidrug efflux pumps, especially that of Cdr1B overexpression, in contributing azole resistance in A. flavus.

scholarly journals Acute lymphoblastic leukemia presenting as nephromegaly in a child: a rare case report

2019 ◽  
Vol 61 (1) ◽  
pp. 97 ◽  
Author(s):  
Shilpa Khanna Arora ◽  
Swarnim Swarnim ◽  
Alok Hemal ◽  
Neha Bidhuri
Keyword(s):  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
Rare Case ◽  
Lymphoblastic Leukemia ◽  
Rare Case Report

scholarly journals Photo Quiz: An Immunosuppressed Acute Lymphoblastic Leukemia Patient with Fever and Lung Nodules

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Luca T. Giurgea ◽  
Jessica L. Dillon ◽  
Laura J. Tafe ◽  
Richard A. Zuckerman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Lung Nodules ◽  
Leukemia Patient
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