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Molecular Diagnostics in Hematologic Malignancies

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Molecular Diagnostics in Cytopathology

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Abstract

In hematologic malignancies, molecular testing of cytology specimens can be extremely useful in the context of tissue-based neoplasms such as lymphomas and myeloid sarcomas when the source of nucleic acids can be limited. FNA specimens are ideal for obtaining unprocessed high-quality nucleic acids essential for simultaneous assessment of a variety of genetic alterations as is usually the case with hematologic malignancies. Concurrent quantitative tumor burden assessed by multiparametric flow cytometry analysis on these samples enables a more informative interpretation of results. Clonality assays to detect monoclonal rearrangements in immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) beta or gamma receptor genes are invaluable for differentiating low-grade B-cell and T-cell lymphoproliferative disorders from reactive conditions. Assessment of characteristic gene translocations and gene mutations is fundamental for subclassification of small B-cell lymphomas and myeloid leukemias and prognostication of large B-cell lymphomas. Estimation of the degree of somatic hypermutation in IGHV is the standard of care for prognostication in CLL/SLL. Gene mutation analysis also affects the choice of therapy by identification of targets for treatment using approved FDA drugs and novel agents in clinical trials. In this context, screening of drug resistance mutations has emerged as a critical aspect of monitoring these patients akin to the assessment of measurable (minimal) residual disease. And lastly, monitoring of cancer-associated viruses such as EBV is crucial in various settings. Further details are elaborated in the chapter below.

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Abbreviations

ABL1 :

ABL proto-oncogene 1

ALCL:

Anaplastic large-cell lymphoma

ALK :

Anaplastic lymphoma kinase or ALK receptor tyrosine kinase

ASXL1 :

Additional sex combs like 1

ATRA:

All-trans-retinoic acid

BCL2/BCL6/BCL10 :

B-cell CLL/lymphoma 2/6/10

BCR:

Breakpoint cluster region

BIRC3 :

Baculoviral IAP repeat-containing protein 3

BRAF :

V-raf murine sarcoma viral oncogene homolog B

BTK :

Bruton tyrosine kinase

CEBPA :

CCAAT-enhancer-binding protein alpha

CHOP:

Cyclophosphamide, hydroxydaunorubicin (doxorubicin or Adriamycin), Oncovin (vincristine), and prednisone

CNS:

Central nervous system

COO:

Cell of origin

CXCR4 :

C-X-C motif chemokine receptor 4

DNA:

Deoxyribonucleic acid

DNMT3A :

DNA methyltransferase 3 alpha

DUSP22 :

Dual specificity phosphatase 22

EBV:

Epstein-Barr virus

FDA:

Food and Drug Administration

FFPE:

Formalin-fixed paraffin-embedded

FISH:

Fluorescence in situ hybridization

FL:

Follicular lymphoma

FLT3 :

Fms-related tyrosine kinase 3

FNA:

Fine-needle aspiration

FOXP1 :

Forkhead box P1

GEP:

Gene expression profile

IDH :

Isocitrate dehydrogenase

IGH:

Immunoglobulin heavy chain locus

IGHV:

Immunoglobulin heavy chain variable region

KIT :

KIT proto-oncogene receptor tyrosine kinase

KRAS :

Kirsten rat sarcoma viral oncogene homolog

MALT1 :

Mucosa-associated lymphoid tissue lymphoma translocation gene 1

MAP2K1 :

Mitogen-activated protein kinase 1

MYC :

V-myc avian myelocytomatosis viral oncogene homolog

MYD88 :

Myeloid differentiation primary response 88

NK:

Natural killer

NGS:

Next-generation sequencing

NOTCH1 :

Notch (Drosophila) homolog 1 (translocation-associated)

NPM1 :

Nucleophosmin 1

PAX-5 :

Paired box 5

PDGFRA :

Platelet-derived growth factor receptor alpha

PLCG2 :

Phospholipase C gamma 2

qPCR:

Quantitative polymerase chain reaction

RUNX1 :

Runt-related transcription factor 1

SF3B1 :

Splicing factor 3b subunit 1

TCL1A :

T-cell leukemia/lymphoma 1A

TCR:

T-cell receptor

TET2 :

Tet methylcytosine dioxygenase 2

TP53/63 :

Tumor protein p53/p63

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Authors and Affiliations

  1. Department of Hematopathology and Molecular Diagnostics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rashmi Kanagal-Shamanna

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  1. Rashmi Kanagal-Shamanna
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Correspondence to Rashmi Kanagal-Shamanna .

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Editors and Affiliations

  1. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    Sinchita Roy-Chowdhuri

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Paul A. VanderLaan

  3. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    John M. Stewart

  4. Department of Laboratory Medicine, University of Toronto, Toronto, ON, Canada

    Gilda da Cunha Santos

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Kanagal-Shamanna, R. (2019). Molecular Diagnostics in Hematologic Malignancies. In: Roy-Chowdhuri, S., VanderLaan, P., Stewart, J., Santos, G. (eds) Molecular Diagnostics in Cytopathology. Springer, Cham. https://doi.org/10.1007/978-3-319-97397-5_17

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