Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia

Staber, Philipp B.; Herling, Marco; Bellido, Mar; Jacobsen, Eric; Davids, Matthew S.; Kadia, Tapan M.; Shustov, Andrei R.; Tournilhac, Olivier; Bachy, Emmanuel; Zaja, Francesco; Porkka, Kimmo; Hoermann, Gregor; Simonitsch‐Klupp, Ingrid; Haferlach, Claudia; Kubicek, Stefan; Mayerhoefer, Marius E.; Hopfinger, Georg; Jaeger, Ulrich; Dearden, Claire

doi:10.1182/blood.2019000402

Cited by 99 publications

(144 citation statements)

References 56 publications

(103 reference statements)

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“…T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy characterized by an expansion of mature T-lymphocytes [1]. Although with an incidence of <2.0/million/year in Western countries infrequently encountered, T-PLL is the most common mature T-cell leukemia [2].…”

Section: Introductionmentioning

confidence: 99%

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

Wahnschaffe

Braun

Timonen

et al. 2019

Cancers

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T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Recent studies detected genomic aberrations affecting JAK and STAT genes in T-PLL. Due to the limited number of primary patient samples available, genomic analyses of the JAK/STAT pathway have been performed in rather small cohorts. Therefore, we conducted-via a primary-data based pipeline-a meta-analysis that re-evaluated the genomic landscape of T-PLL. It included all available data sets with sequence information on JAK or STAT gene loci in 275 T-PLL. We eliminated overlapping cases and determined a cumulative rate of 62.1% of cases with mutated JAK or STAT genes. Most frequently, JAK1 (6.3%), JAK3 (36.4%), and STAT5B (18.8%) carried somatic single-nucleotide variants (SNVs), with missense mutations in the SH2 or pseudokinase domains as most prevalent. Importantly, these lesions were predominantly subclonal. We did not detect any strong association between mutations of a JAK or STAT gene with clinical characteristics. Irrespective of the presence of gain-of-function (GOF) SNVs, basal phosphorylation of STAT5B was elevated in all analyzed T-PLL. Fittingly, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses (in 71.4% of T-PLL in total, in 68.4% of T-PLL without any JAK or STAT mutations). They included DUSP4, CD45, TCPTP, SHP1, SOCS1, SOCS3, and HDAC9.Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity. In essence, we present a comprehensive meta-analysis on the highly prevalent genomic lesions that affect genes encoding JAK/STAT signaling components. This provides an overview of possible modes of activation of this pathway in a large cohort of T-PLL. In light of new advances in JAK/STAT inhibitor development, we also outline translational contexts for harnessing active JAK/STAT signaling, which has emerged as a 'secondary' hallmark of T-PLL.

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Section: Introductionmentioning

confidence: 99%

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

Wahnschaffe

Braun

Timonen

et al. 2019

Cancers

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“…The skin is involved in ~20% of cases and may have an erythematous or papular appearance. 3,4,6 Consensus criteria have recently been proposed in an effort to more precisely define the diagnosis, for T‐PLL, which are summarized in Table 1 7 …”

Section: Clinical Presentationmentioning

confidence: 99%

“…A clonal T‐cell receptor gene rearrangement may be detected using polymerase chain reaction (PCR), next‐generation sequencing (NGS), or flow cytometric Vβ analysis 7 . In addition, up to 80% of cases of T‐PLL have complex karyotypic abnormalities which can aid in classification of this malignancy.…”

Section: Molecular Biology Of T‐pllmentioning

confidence: 99%

T‐cell prolymphocytic leukemia: Review of an entity and its differential diagnostic considerations

Frater

2020

Int J Lab Hematology

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T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell leukemia characterized in many patients by marked peripheral lymphocytosis, prominent splenomegaly, and skin lesions. The differential diagnosis is broad and includes other T-cell disorders presenting with similar clinical findings. This review addresses (a) the natural history, demographics, and genetic features of T-PLL; (b) clinical and pathologic differential diagnostic considerations; and (c) recent developments in the T-PLL literature relevant to laboratory professionals. K E Y W O R D S leukemia, morphology, T-cells

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“…Stephen M. Ansell | Mayo Clinic Blocking programmed death 1 (PD-1) signaling in relapsed Hodgkin lymphoma results in high response rates, [1][2][3] and Chen et al, in this issue of Blood, report the outcome of patients treated with pembrolizumab with 2 years of follow-up. 4 They confirm that responses in patients treated with this PD-1-blocking antibody are durable and find that patients continue to tolerate PD-1 blockade well with extended treatment.…”

Section: Pembrolizumab: Living Up To Expectationsmentioning

confidence: 99%

“…The use of monoclonal antibodies targeting PD-1 in patients with Hodgkin lymphoma has resulted in high response rates, even in patients who have had multiple lines of therapy, including the use of stem cell transplantation and the antibody-drug conjugate brentuximab vedotin. [1][2][3] Although the high response rates initially reported with pembrolizumab were very encouraging, longer follow-up was required to determine whether the responses would be durable in all groups of patients treated. In this study with 2 years of follow-up, responses persisted in all groups of patients, including those with primary refractory disease unable to proceed to an autologous transplant.…”

Section: Pembrolizumab: Living Up To Expectationsmentioning

confidence: 99%