How T-lymphoblastic leukemia can be classified based on genetics using standard diagnostic techniques enhanced by whole genome sequencing

Müller, Janine; Walter, Wencke; Haferlach, Claudia; Müller, Heiko; Fuhrmann, Irene; Müller, Martha‐Lena; Ruge, Henning; Meggendorfer, Manja; Kern, Wolfgang; Haferlach, Torsten; Stengel, Anna

doi:10.1038/s41375-022-01743-6

Cited by 6 publications

(5 citation statements)

References 12 publications

(12 reference statements)

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“…In the BCL11B group, NOTCH1 mutations, PHF6 mutations, and CDKN2A deletions were absent, and FLT3 mutations were frequent (7/10 cases, 70%), including both internal tandem duplication and tyrosine kinase domain mutations. There was a high expression of KIT and LMO2, low RAG1 and RAG2 expression, and TCR rearrangements were absent [165]. Their findings supported the hypothesis that the BCL11B type of T-ALL arises from a hematopoietic progenitor stem cell expressing ectopic BCL11B, which induces the T-lineage commitment in neoplastic cells [165,166].…”

Section: T-all Not Otherwise Specifiedsupporting

confidence: 66%

“…There was a high expression of KIT and LMO2, low RAG1 and RAG2 expression, and TCR rearrangements were absent [165]. Their findings supported the hypothesis that the BCL11B type of T-ALL arises from a hematopoietic progenitor stem cell expressing ectopic BCL11B, which induces the T-lineage commitment in neoplastic cells [165,166]. BCL11B rearrangements are found in T-ALL, mixed-phenotype acute leukemia, and immature acute myeloid leukemia [166,167].…”

Section: T-all Not Otherwise Specifiedsupporting

confidence: 62%

“…The abnormalities that still could not be identified by these standard techniques were identified by WGS, which also confirmed all abnormalities detected by the traditional methods. Rearrangements of BCL11B::TLX3, SET::NUP214, and STIL::TAL1 were not detectable by chromosome banding analysis due to the low resolution of the technique [165]. The BCL11B group showed more frequent granulocyte/macrophage progenitor and hematopoietic stem cells than the TLX1, TLX3, and TAL1 groups, which showed more frequent dendritic cells, Th1, and Th2 cells.…”

Section: T-all Not Otherwise Specifiedmentioning

confidence: 93%

“…Significantly, in late-2022, standard genetic techniques (chromosomal banding analysis, FISH, and molecular genetic analysis by reverse-transcriptase PCR, combined with whole-genome sequencing) classified T-ALL into nine distinct subgroups based on genetic alterations in TLX1, TLX3, TAL1, HOXA9/10, MLLT10, NUP98, MYB, BCL11B, and the presence of SET::NUP214 fusion gene [165]. These genetic subgroups of T-ALL defined by standard cytogenetic techniques and whole genome sequencing are shown in Table 3, modified from Müller et al 2023 [165].…”

Section: T-all Not Otherwise Specifiedmentioning

confidence: 99%

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Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 2: B-/T-Cell Acute Lymphoblastic Leukemias

Kansal

2023

Lymphatics

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The diagnosis and treatment of lymphoid neoplasms have undergone a continuously progressive positive change in the last three decades, with accelerated progress in the previous decade due to the advent of genomics in cancer diagnosis. Significantly, there has been an increasing emphasis on integrating molecular genetics with clinical, morphological, immunophenotypic, and cytogenetic evaluation for diagnosis. As we think of moving forward with further advances in the genomics era, it will be first helpful to understand our current state of knowledge and how we achieved it in the challenging and complex field of lymphoid neoplasms, which comprise very heterogeneous neoplastic diseases in children and adults, including clinically acute lymphoblastic leukemias (ALLs) arising from precursor lymphoid cells and clinically indolent and aggressive lymphomas arising from mature lymphoid cells. This work aims to provide an overview of the historical evolution and the current state of knowledge to anyone interested in the field of lymphoid neoplasms, including students, physicians, and researchers. Therefore, I have discussed this complex topic in three review manuscripts, designated Parts 1–3. In Part 1, I explain the basis of the diagnostic classification of lymphoid neoplasms and its evolution up to the current fifth edition of the World Health Organization classification of hematolymphoid neoplasms and the crucial importance of diagnostic tumor classifications in achieving and advancing patient care and precision medicine. In the second and third manuscripts, I discuss current diagnostic considerations for B-ALL and T-ALL (Part 2) and common indolent and aggressive mature leukemias/lymphomas (Part 3), including significant updates in the WHO 2022 classification, newly described entities, and concepts, including genetic predisposition to ALLs and lymphomas, and emphasizing throughout the essential integration of molecular genetics with clinical, morphologic, immunophenotypic, and cytogenetic evaluation, as required for the precise diagnosis of the type of lymphoma/leukemia in any patient.

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Section: T-all Not Otherwise Specifiedsupporting

confidence: 66%

Section: T-all Not Otherwise Specifiedsupporting

confidence: 62%

Section: T-all Not Otherwise Specifiedmentioning

confidence: 93%

Section: T-all Not Otherwise Specifiedmentioning

confidence: 99%

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Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 2: B-/T-Cell Acute Lymphoblastic Leukemias

Kansal

2023

Lymphatics

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“…Classifying T-ALL on a molecular level remains challenging and thus molecular subgroups have not yet been incorporated into the classifications of WHO and only as provisional entities in the International Consensus Classification [ 16 , 18 ]. Eight provisional subentities have been proposed in the International Consensus Classification [ 16 ] and a diagnostic approach using whole genome sequencing has been proposed [ 32 ]. Although it is obvious that dysregulations of certain oncogenes, partly based on common genetic alterations, drive specific T-ALL phenotypes, the exact definitions of subgroups are a matter of debate, in particular in adult patients.…”

Section: Discussionmentioning

confidence: 99%

Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols

Neumann,

Beder,

Bastian

et al. 2024

Leukemia

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In contrast to B-cell precursor acute lymphoblastic leukemia (ALL), molecular subgroups are less well defined in T-lineage ALL. Comprehensive studies on molecular T-ALL subgroups have been predominantly performed in pediatric ALL patients. Currently, molecular characteristics are rarely considered for risk stratification. Herein, we present a homogenously treated cohort of 230 adult T-ALL patients characterized on transcriptome, and partly on DNA methylation and gene mutation level in correlation with clinical outcome. We identified nine molecular subgroups based on aberrant oncogene expression correlating to four distinct DNA methylation patterns. The subgroup distribution differed from reported pediatric T-ALL cohorts with higher frequencies of prognostic unfavorable subgroups like HOXA or LYL1/LMO2. A small subset (3%) of HOXA adult T-ALL patients revealed restricted expression of posterior HOX genes with aberrant activation of lncRNA HOTTIP. With respect to outcome, TLX1 (n = 44) and NKX2-1 (n = 4) had an exceptionally favorable 3-year overall survival (3y-OS) of 94%. Within thymic T-ALL, the non TLX1 patients had an inferior but still good prognosis. To our knowledge this is the largest cohort of adult T-ALL patients characterized by transcriptome sequencing with meaningful clinical follow-up. Risk classification based on molecular subgroups might emerge and contribute to improvements in outcome.

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Clinicopathologic features and outcomes of acute leukemia harboring PICALM::MLLT10 fusion

Wang,

Zhang,

et al. 2024

Human Pathology

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How T-lymphoblastic leukemia can be classified based on genetics using standard diagnostic techniques enhanced by whole genome sequencing

Cited by 6 publications

References 12 publications

Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 2: B-/T-Cell Acute Lymphoblastic Leukemias

Diagnosis and Molecular Pathology of Lymphoblastic Leukemias and Lymphomas in the Era of Genomics and Precision Medicine: Historical Evolution and Current Concepts—Part 2: B-/T-Cell Acute Lymphoblastic Leukemias

Molecular subgroups of T-cell acute lymphoblastic leukemia in adults treated according to pediatric-based GMALL protocols

Clinicopathologic features and outcomes of acute leukemia harboring PICALM::MLLT10 fusion

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