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Blood Oct 2019T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will... (Review)
Review
T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of patients with T-PLL, it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL, and will thus support clinical decision making, as well as the approval of new therapeutics by healthcare authorities.
Topics: Bone Marrow; Disease Management; Gene Expression Regulation, Leukemic; Humans; Immunophenotyping; Leukemia, Prolymphocytic, T-Cell; Mutation; Neoplasm Staging; T-Lymphocytes
PubMed: 31292114
DOI: 10.1182/blood.2019000402 -
International Journal of Molecular... Jul 2023T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia,... (Review)
Review
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. In 2019, the T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis, staging, and assessment of response to treatment of T-PLL with the goal of harmonizing research efforts and supporting clinical decision-making. T-PLL pathogenesis is commonly driven by T-cell leukemia 1 () overexpression and loss, genetic alterations that are incorporated into the TPLL-ISG diagnostic criteria. The cooperativity between family members and is seemingly unique to T-PLL across the spectrum of T-cell neoplasms. The role of the T-cell receptor, its downstream kinases, and JAK/STAT signaling are also emerging themes in disease pathogenesis and have obvious therapeutic implications. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review.
Topics: Humans; Leukemia, Prolymphocytic, T-Cell; Alemtuzumab; Hematopoietic Stem Cell Transplantation; Mutation
PubMed: 37569479
DOI: 10.3390/ijms241512106 -
Cureus Feb 2021T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell hematologic neoplasm with a very poor prognosis and limited treatment options to date. Single-agent... (Review)
Review
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T-cell hematologic neoplasm with a very poor prognosis and limited treatment options to date. Single-agent alemtuzumab remains the first line of therapy for the treatment-naive and relapsed/refractory patients. Prospective clinical trials are difficult to conduct given that these patients have a short life expectancy after the initial diagnosis. As a result, researchers are implementing the use of targeted therapies in vitro and ex vivo followed by in vivo trials on a small subset of patients which are reviewed here. Newer approaches in the treatment of T-PLL are developing based on recognizing the cytogenetic phenotype of each patient and targeting the identified defective genes that are usually involved in the cell cycle regulation such as protooncogenes, tumor suppressors, and deoxyribonucleic acid (DNA) repair genes. These could potentially redirect the management in the near future and improve the overall survival (OS) and the progression-free survival (PFS) for these patients.
PubMed: 33728186
DOI: 10.7759/cureus.13237 -
Frontiers in Oncology 2022T-cell clones can frequently be identified in peripheral blood. It can be difficult to appreciate whether these are benign and transient or whether they signify a clonal... (Review)
Review
T-cell clones can frequently be identified in peripheral blood. It can be difficult to appreciate whether these are benign and transient or whether they signify a clonal disorder. We review factors that aid in understanding the relevance of T-cell clones. Conversely, obvious pathological T-cell clones can be detected in blood, but there is uncertainty in how to categorize this clonal T cell population, thus, we adopt a multidisciplinary review of the clinical features, diagnostic material and radiology before making the diagnosis. In this review we shall discuss some of these challenges faced when diagnosing mature T-cell leukemias.
PubMed: 35359424
DOI: 10.3389/fonc.2022.777066 -
Blood Dec 1991
Topics: Humans; Immunophenotyping; Leukemia, Prolymphocytic; T-Lymphocytes
PubMed: 1742477
DOI: No ID Found -
Oncotarget May 2023
Topics: Humans; Leukemia, Prolymphocytic, T-Cell
PubMed: 37141408
DOI: 10.18632/oncotarget.28378 -
Best Practice & Research. Clinical... Sep 2019Genomic analysis of cancer offers the hope of identifying new treatments or aiding in the selection of existing treatments. Rare leukemias pose additional challenges in... (Review)
Review
Genomic analysis of cancer offers the hope of identifying new treatments or aiding in the selection of existing treatments. Rare leukemias pose additional challenges in this regard as samples may be hard to acquire and when found the underlying pathway may not be attractive to drug development since so few individuals are affected. In this case, it can be useful to identify common mutational overlap among subsets of rare leukemias to increase the number of individuals that may benefit from a targeted therapy. This chapter examines the current mutational landscape of large granular lymphocyte (LGL) leukemia with a focus on STAT3 mutations, the most common mutation in LGL leukemia to date. We examined the linkage between these mutations and autoimmune symptoms and disorders, in cases of obvious and suspected LGL leukemia. We then summarized and compared mutations in a set of other rare leukemias that also have JAK/STAT signaling pathway activation brought about by genomic changes. These include T-cell acute lymphoblastic leukemia (T-ALL), T-cell prolymphocytic leukemia (T-PLL), cutaneous T-cell lymphoma (CTCL), select peripheral T-cell lymphoma (PTCL), and adult T-cell leukemia/lymphoma (ATLL). Though STAT3 activation is common in these leukemias, the way in which it is achieved, such as the activating cytokine pathway and/or the co-mutational background, is quite diverse.
Topics: Genomics; Humans; Leukemia, Large Granular Lymphocytic; Leukemia-Lymphoma, Adult T-Cell; Mutation; Rare Diseases; STAT3 Transcription Factor
PubMed: 31585620
DOI: 10.1016/j.beha.2019.06.003