Recent advances in T-cell lymphoid neoplasms

Bigas, Anna; Rodríguez‐Sevilla, Juan José; Espinosa, Lluís; Gallardo, Fernando

doi:10.1016/j.exphem.2021.12.191

Cited by 14 publications

(11 citation statements)

References 241 publications

(260 reference statements)

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“…ALL is a highly heterogeneous disease, displaying a variety of genomic and chromosomic alterations including aneuploidies, translocations, alterations in the number of copies of DNA fragments, and mutations. T-ALL is an aggressive variant characterized by the uncontrolled proliferation of T-type lymphoblasts that arise in the thymus and express markers for immature T-lymphocytes, which accumulate in the blood [ 114 ]. B-ALL is characterized by the production of B-lymphocyte precursor cells that are produced in the marrow and accumulate in the blood.…”

Section: Autophagy In Hematological Malignanciesmentioning

confidence: 99%

“…Anaplastic large-cell lymphoma (ALCL) is a rare type of T-NHL that comprises about <5% of all NHLs [ 207 ]. It is an aggressive form of malignant lymphoma that affects mostly children and young adults [ 114 ]. There are two systemic forms of ALCL, depending on the presence of absence of aberrant anaplastic lymphoma kinase (ALK) expression, carrying translocations at the 2p23 region.…”

Section: Autophagy In Hematological Malignanciesmentioning

confidence: 99%

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Autophagy in Hematological Malignancies

Ruiz

Sánchez-Maldonado

Nevot

et al. 2022

Cancers

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Autophagy is a highly conserved metabolic pathway via which unwanted intracellular materials, such as unfolded proteins or damaged organelles, are digested. It is activated in response to conditions of oxidative stress or starvation, and is essential for the maintenance of cellular homeostasis and other vital functions, such as differentiation, cell death, and the cell cycle. Therefore, autophagy plays an important role in the initiation and progression of tumors, including hematological malignancies, where damaged autophagy during hematopoiesis can cause malignant transformation and increase cell proliferation. Over the last decade, the importance of autophagy in response to standard pharmacological treatment of hematological tumors has been observed, revealing completely opposite roles depending on the tumor type and stage. Thus, autophagy can promote tumor survival by attenuating the cellular damage caused by drugs and/or stabilizing oncogenic proteins, but can also have an antitumoral effect due to autophagic cell death. Therefore, autophagy-based strategies must depend on the context to create specific and safe combination therapies that could contribute to improved clinical outcomes. In this review, we describe the process of autophagy and its role on hematopoiesis, and we highlight recent research investigating its role as a potential therapeutic target in hematological malignancies. The findings suggest that genetic variants within autophagy-related genes modulate the risk of developing hemopathies, as well as patient survival.

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Section: Autophagy In Hematological Malignanciesmentioning

confidence: 99%

Section: Autophagy In Hematological Malignanciesmentioning

confidence: 99%

Autophagy in Hematological Malignancies

Ruiz

Sánchez-Maldonado

Nevot

et al. 2022

Cancers

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“…As many of these genetic abnormalities are shared by other different hematological neoplasms, they may represent clear candidates for genetic screening panel designs of T-cell NHL to improve diagnosis or monitoring ( Table 2 ) [ 30 ].…”

Section: Primary Cutaneous T-cell Lymphomas: Mycosis Fungoides and Sé...mentioning

confidence: 99%

Genetics Abnormalities with Clinical Impact in Primary Cutaneous Lymphomas

Gallardo

Pujol

2022

Cancers

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Primary cutaneous lymphomas comprise a heterogeneous group of extranodal non-Hodgkin lymphomas (NHL) that arise from skin resident lymphoid cells and are manifested by specific lymphomatous cutaneous lesions with no evidence of extracutaneous disease at the time of diagnosis. They may originate from mature T-lymphocytes (70% of all cases), mature B-lymphocytes (25–30%) or, rarely, NK cells. Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of T-cell malignancies including Mycosis Fungoides (MF) the most frequent subtype, accounting for approximately half of CTCL, and Sézary syndrome (SS), which is an erythrodermic and leukemic subtype characterized by significant blood involvement. The mutational landscape of MF and SS by NGS include recurrent genomic alterations in the TCR signaling effectors (i.e., PLCG1), the NF-κB elements (i.e., CARD11), DNA damage/repair elements (TP53 or ATM), JAK/STAT pathway elements or epigenetic modifiers (DNMT3). Genomic copy number variations appeared to be more prevalent than somatic mutations. Other CTCL subtypes such as primary cutaneous anaplastic large cell lymphoma also harbor genetic alterations of the JAK/STAT pathway in up to 50% of cases. Recently, primary cutaneous aggressive epidermotropic T-cell lymphoma, a rare fatal subtype, was found to contain a specific profile of JAK2 rearrangements. Other aggressive cytotoxic CTCL (primary cutaneous γδ T-cell lymphomas) also show genetic alterations in the JAK/STAT pathway in a large proportion of patients. Thus, CTCL patients have a heterogeneous genetic/transcriptional and epigenetic background, and there is no uniform treatment for these patients. In this scenario, a pathway-based personalized management is required. Cutaneous B-cell lymphoma (CBCL) subtypes present a variable genetic profile. The genetic heterogeneity parallels the multiple types of specialized B-cells and their specific tissue distribution. Particularly, many recurrent hotspot and damaging mutations in primary cutaneous diffuse large B-cell lymphoma of the leg type, involving MYD88 gene, or BCL6 and MYC translocations and BLIMP1 or CDKN2A deletions are useful for diagnostic and prognostic purposes for this aggressive subtype from other indolent CBCL forms.

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“…Indeed, drugs targeting specific pathways such as NOTCH, Jak/Stat, and PI3K are being researched and tested in T-ALL patients. 14 In these few cancer examples, a common thread is that the oncogenic pathways driving these diseases are highly mutagenic, have been difficult to target effectively with current drug types, and they influence several other pro-oncogenic pathways. New and specific therapies that correct the mutations at the DNA level such as viral-based gene therapies could be incredibly impactful as a treatment.…”

Section: Introductionmentioning

confidence: 99%