Visceral Leishmaniasis With Associated Immune Dysregulation Leading to Lymphoma

Osakwe, Nwamaka M.; Paulus, Andrew; Haggerty, Paul; Wood, Roger A.; Becker, Sara; Weina, Peter J.; Dolan, Matthew J.; Prakash, Vidhya

doi:10.7205/milmed-d-12-00407

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…In fact, four different association between these diseases have been described: (a) leishmaniasis mimicking malignancy [ 10 , 11 , 12 , 13 ]; (b) leishmaniasis arising from difficulty diagnosing and treating infection among patients receiving chemotherapy for various malignant disorders [ 14 , 15 ]; (c) simultaneous diagnosis of leishmaniasis and a neoplastic disorder in the same tissue samples of patients [ 16 , 17 , 18 ]; and (d) direct involvement of Leishmania spp. in the pathogenesis of malignant lesions, especially skin and mucous membrane tumors [ 19 , 20 , 21 , 22 ]. In addition to these associations, the similarities between tumor cells and parasites were largely mentioned when studying expressed proteins and potential therapeutic targets [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells

Larrea

Fernández-Rubio

Peña-Guerrero

et al. 2022

IJMS

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Around 15% of cancer cases are attributable to infectious agents. Epidemiological studies suggest that an association between leishmaniasis and cancer does exist. Recently, the homologue of PES1 in Leishmania major (LmjPES) was described to be involved in parasite infectivity. Mammalian PES1 protein has been implicated in cellular processes like cell cycle regulation. Its BRCT domain has been identified as a key factor in DNA damage-responsive checkpoints. This work aimed to elucidate the hypothetical oncogenic implication of BRCT domain from LmjPES in host cells. We generated a lentivirus carrying this BRCT domain sequence (lentiBRCT) and a lentivirus expressing the luciferase protein (lentiLuc), as control. Then, HEK293T and NIH/3T3 mammalian cells were infected with these lentiviruses. We observed that the expression of BRCT domain from LmjPES conferred to mammal cells in vitro a greater replication rate and higher survival. In in vivo experiments, we observed faster tumor growth in mice inoculated with lentiBRCT respect to lentiLuc HEK293T infected cells. Moreover, the lentiBRCT infected cells were less sensitive to the genotoxic drugs. Accordingly, gene expression profiling analysis revealed that BRCT domain from LmjPES protein altered the expression of proliferation- (DTX3L, CPA4, BHLHE41, BMP2, DHRS2, S100A1 and PARP9), survival- (BMP2 and CARD9) and chemoresistance-related genes (DPYD, Dok3, DTX3L, PARP9 and DHRS2). Altogether, our results reinforced the idea that in eukaryotes, horizontal gene transfer might be also achieved by parasitism like Leishmania infection driving therefore to some crucial biological changes such as proliferation and drug resistance.

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Section: Introductionmentioning

confidence: 99%

The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells

Larrea

Fernández-Rubio

Peña-Guerrero

et al. 2022

IJMS

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“…Furthermore, the atypical manifestations of VL are described and mainly characterized by diffuse enlargement of lymph nodes and associated with lymphomas. The similarity of symptoms between hematological disorders and VL, as well as the atypical presentations of VL, associated with lymphomas make its diagnosis difficult 12 , 13 .…”

Section: Discussionmentioning

confidence: 99%

Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin’s lymphoma

Pôrto¹,

Carvalho²,

Buzo³

et al. 2022

Rev. Inst. Med. trop. S. Paulo

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Visceral leishmaniasis (VL) is mainly caused by Leishmania (Leishmania) donovani and Leishmania (L.) infantum ; however, other Leishmania species have been associated with VL. We report a case of a patient simultaneously diagnosed with VL caused by Leishmania (L.) amazonensis and Hodgkin’s lymphoma. After treatment with liposomal amphotericin B and chemotherapy, the patient presented a clinical cure. This case report reinforces the hypothesis that other Leishmania species can cause visceral lesions mainly related to immunosuppression.

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“…On the other hand, VL can be synchronously associated with solid tumors, including lymphoma, or can result in an extreme immune dysregulation leading to lymphoproliferative disorders. 17,18 Considering the recurrence of symptoms and still-enlarged lymph nodes, the patient underwent another lymph node biopsy and the hypothesis of malignancy was discarded once again.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient

Vechi

Sousa²,

Cunha

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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In immunocompromised patients, visceral leishmaniasis (VL) can present with atypical clinical symptoms that include poor response to treatment. No optimal therapeutic regimen is available for such cases. In a splenectomized male patient, we observed a disseminated form of the disease in the liver, bone marrow, lymph nodes, and gastrointestinal tract. There was an apparent clinical improvement when he was initially treated with liposomal amphotericin B (L-AmB), but this was followed by a relapse involving severe clinical symptoms. He was finally treated successfully with a combination of L-AmB, meglumine antimoniate, and pentamidine isethionate. It is important to include asplenia as an immunosuppressive condition that induces exotic VL pathologies. In such cases, combination anti-Leishmania drug therapy should be considered.

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Visceral Leishmaniasis With Associated Immune Dysregulation Leading to Lymphoma

Cited by 6 publications

References 16 publications

The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells

The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells

Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin’s lymphoma

Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient

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