SpringerLink
Log in

Molecular Biomarkers in Hematopoietic Neoplasms

  • Chapter
  • First Online:
Molecular Cytopathology

Part of the book series: Essentials in Cytopathology ((EICP,volume 26))

  • 924 Accesses

Abstract

Hematologic malignancies are increasingly recognized as genetic diseases, with precise entity-defining molecular alterations progressively splitting diagnostic categories into narrower subsets. While traditional clinical and morphologic evaluation still underpins the initial approach to hematological disease, newer immunologic, genetic, and molecular modalities are currently critical for accurate categorization.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 49.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Hehn ST, Grogan TM, Miller TP. Utility of fine-needle aspiration as a diagnostic technique in lymphoma. J Clin Oncol. 2004;22(15):3046–52.

    Article  PubMed  Google Scholar 

  2. Katz RL. Controversy in fine-needle aspiration of lymph nodes. A territorial imperative? Am J Clin Pathol. 1997;108(4 Suppl 1):S3–5.

    CAS  PubMed  Google Scholar 

  3. Sandhaus LM. Fine-needle aspiration cytology in the diagnosis of lymphoma. The next step. Am J Clin Pathol. 2000;113(5):623–7.

    Article  CAS  PubMed  Google Scholar 

  4. Frable WJ. Fine-needle aspiration biopsy: a review. Hum Pathol. 1983;14(1):9–28.

    Article  CAS  PubMed  Google Scholar 

  5. Lowhagen T, et al. Aspiration biopsy cytology (ABC) in nodules of the thyroid gland suspected to be malignant. Surg Clin North Am. 1979;59(1):3–18.

    Article  CAS  PubMed  Google Scholar 

  6. Anderson JB, Webb AJ. Fine-needle aspiration biopsy and the diagnosis of thyroid cancer. Br J Surg. 1987;74(4):292–6.

    Article  CAS  PubMed  Google Scholar 

  7. Avent J. Flow cytometry in body fluid analysis. Clin Lab Med. 1985;5(2):389–403.

    CAS  PubMed  Google Scholar 

  8. Craig FE, Foon KA. Flow cytometric immunophenoty** for hematologic neoplasms. Blood. 2008;111(8):3941–67.

    Article  CAS  PubMed  Google Scholar 

  9. Barrena S, et al. Flow cytometry immunophenoty** of fine-needle aspiration specimens: utility in the diagnosis and classification of non-Hodgkin lymphomas. Histopathology. 2011;58(6):906–18.

    Article  PubMed  Google Scholar 

  10. Yu GH, et al. Use of flow cytometry in the diagnosis of lymphoproliferative disorders in fluid specimens. Diagn Cytopathol. 2014;42(8):664–70.

    Article  PubMed  Google Scholar 

  11. Ahluwalia MS, Wallace PK, Peereboom DM. Flow cytometry as a diagnostic tool in lymphomatous or leukemic meningitis: ready for prime time? Cancer. 2012;118(7):1747–53.

    Article  PubMed  Google Scholar 

  12. Bigner SH. Cerebrospinal fluid (CSF) cytology: current status and diagnostic applications. J Neuropathol Exp Neurol. 1992;51(3):235–45.

    Article  CAS  PubMed  Google Scholar 

  13. Bromberg JE, et al. CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies. Neurology. 2007;68(20):1674–9.

    Article  CAS  PubMed  Google Scholar 

  14. Gondos B, King EB. Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques. Acta Cytol. 1976;20(6):542–7.

    CAS  PubMed  Google Scholar 

  15. French CA, et al. Diagnosing lymphoproliferative disorders involving the cerebrospinal fluid: increased sensitivity using flow cytometric analysis. Diagn Cytopathol. 2000;23(6):369–74.

    Article  CAS  PubMed  Google Scholar 

  16. Roma AA, et al. Lymphoid and myeloid neoplasms involving cerebrospinal fluid: comparison of morphologic examination and immunophenoty** by flow cytometry. Diagn Cytopathol. 2002;27(5):271–5.

    Article  PubMed  Google Scholar 

  17. Kraan J, et al. Flow cytometric immunophenoty** of cerebrospinal fluid. Curr Protoc Cytom. 2008. Chapter 6: p. Unit 6 25.

    Google Scholar 

  18. Chan WC, Greiner TC, Bagg A. Molecular diagnosis in hematopathology. In: Jaffe ES et al., editors. Hematopathology. Philadelphia: Elsevier; 2011. p. 56–80.

    Chapter  Google Scholar 

  19. Gold B, et al. Diagnosis of Fragile X syndrome by Southern blot hybridization using a chemiluminescent probe: a laboratory protocol. Mol Diagn. 2000;5(3):169–78.

    Article  CAS  PubMed  Google Scholar 

  20. Bagg A, et al. Immunoglobulin heavy chain gene analysis in lymphomas: a multi-center study demonstrating the heterogeneity of performance of polymerase chain reaction assays. J Mol Diagn. 2002;4(2):81–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pai RK, et al. B-cell clonality determination using an immunoglobulin kappa light chain polymerase chain reaction method. J Mol Diagn. 2005;7(2):300–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. van Dongen JJ, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17(12):2257–317.

    Article  PubMed  Google Scholar 

  23. Sandberg Y, et al. BIOMED-2 multiplex immunoglobulin/T-cell receptor polymerase chain reaction protocols can reliably replace Southern blot analysis in routine clonality diagnostics. J Mol Diagn. 2005;7(4):495–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Evans PA, et al. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21(2):207–14.

    Article  CAS  PubMed  Google Scholar 

  25. Merker JD, Arber DA. Molecular diagnostics of hematopoietic disorders. In: Grody WW et al., editors. Molecular diagnostics: techniques and applications for the clinical laboratory. London: Elsevier; 2010. p. 243–60.

    Chapter  Google Scholar 

  26. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281(5381):1322–6.

    Article  CAS  PubMed  Google Scholar 

  27. Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116(2):205–19.

    Article  CAS  PubMed  Google Scholar 

  28. Vega F, Medeiros LJ. Chromosomal translocations involved in non-Hodgkin lymphomas. Arch Pathol Lab Med. 2003;127(9):1148–60.

    CAS  PubMed  Google Scholar 

  29. Bertoni F, Zucca E, Cotter FE. Molecular basis of mantle cell lymphoma. Br J Haematol. 2004;124(2):130–40.

    Article  CAS  PubMed  Google Scholar 

  30. Sherr CJ. The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 2000;60(14):3689–95.

    CAS  PubMed  Google Scholar 

  31. Belaud-Rotureau MA, et al. A comparative analysis of FISH, RT-PCR, PCR, and immunohistochemistry for the diagnosis of mantle cell lymphomas. Mod Pathol. 2002;15(5):517–25.

    Article  PubMed  Google Scholar 

  32. Remstein ED, et al. Diagnostic utility of fluorescence in situ hybridization in mantle-cell lymphoma. Br J Haematol. 2000;110(4):856–62.

    Article  CAS  PubMed  Google Scholar 

  33. Du MQ. MALT lymphoma: recent advances in aetiology and molecular genetics. J Clin Exp Hematop. 2007;47(2):31–42.

    Article  PubMed  Google Scholar 

  34. Remstein ED, James CD, Kurtin PJ. Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. Am J Pathol. 2000;156(4):1183–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Remstein ED, et al. Primary pulmonary MALT lymphomas show frequent and heterogeneous cytogenetic abnormalities, including aneuploidy and translocations involving API2 and MALT1 and IgH and MALT1. Leukemia. 2004;18(1):156–60.

    Article  CAS  PubMed  Google Scholar 

  36. Remstein ED, et al. The incidence and anatomic site specificity of chromosomal translocations in primary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in North America. Am J Surg Pathol. 2006;30(12):1546–53.

    Article  PubMed  Google Scholar 

  37. Streubel B, et al. Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites. Leukemia. 2004;18(10):1722–6.

    Article  CAS  PubMed  Google Scholar 

  38. Liu H, et al. Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet. 2001;357(9249):39–40.

    Article  CAS  PubMed  Google Scholar 

  39. Damle RN, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94(6):1840–7.

    CAS  PubMed  Google Scholar 

  40. Hamblin TJ, et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848–54.

    CAS  PubMed  Google Scholar 

  41. Rosenwald A, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med. 2001;194(11):1639–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Moreno C, Montserrat E. New prognostic markers in chronic lymphocytic leukemia. Blood Rev. 2008;22(4):211–9.

    Article  CAS  PubMed  Google Scholar 

  43. Seiler T, Döhner H, Stilgenbauer S. Risk stratification in chronic lymphocytic leukemia. Semin Oncol. 2006;33(2):186–94.

    Article  CAS  PubMed  Google Scholar 

  44. Dohner H, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910–6.

    Article  CAS  PubMed  Google Scholar 

  45. Kröber A, et al. Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol. 2006;24(6):969–75.

    Article  PubMed  Google Scholar 

  46. Garcia-Marco J, et al. Trisomy 12 in B-cell chronic lymphocytic leukaemia: assessment of lineage restriction by simultaneous analysis of immunophenotype and genotype in interphase cells by fluorescence in situ hybridization. Br J Haematol. 1994;87(1):44–50.

    Article  CAS  PubMed  Google Scholar 

  47. Dicker F, et al. The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype. Leukemia. 2009;23(1):117–24.

    Article  CAS  PubMed  Google Scholar 

  48. Fabris S, et al. Molecular and transcriptional characterization of 17p loss in B-cell chronic lymphocytic leukemia. Genes Chromosomes Cancer. 2008;47(9):781–93.

    Article  CAS  PubMed  Google Scholar 

  49. Zenz T, et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood. 2008;112(8):3322–9.

    Article  CAS  PubMed  Google Scholar 

  50. Calin GA, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Blum KA, Lozanski G, Byrd JC. Adult Burkitt leukemia and lymphoma. Blood. 2004;104(10):3009–20.

    Article  CAS  PubMed  Google Scholar 

  52. Hecht JL, Aster JC. Molecular biology of Burkitt’s lymphoma. J Clin Oncol. 2000;18(21):3707–21.

    CAS  PubMed  Google Scholar 

  53. Amati B, et al. Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell. 1993;72(2):233–45.

    Article  CAS  PubMed  Google Scholar 

  54. Patte C, et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. 2007;109(7):2773–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Chen W, et al. Heterologous promoters fused to BCL6 by chromosomal translocations affecting band 3q27 cause its deregulated expression during B-cell differentiation. Blood. 1998;91(2):603–7.

    CAS  PubMed  Google Scholar 

  56. Boerma EG, et al. Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of today’s knowledge. Leukemia. 2009;23(2):225–34.

    Article  CAS  PubMed  Google Scholar 

  57. Haralambieva E, et al. Clinical, immunophenotypic, and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma. Am J Surg Pathol. 2005;29(8):1086–94.

    PubMed  Google Scholar 

  58. McClure RF, et al. Adult B-cell lymphomas with Burkitt-like morphology are phenotypically and genotypically heterogeneous with aggressive clinical behavior. Am J Surg Pathol. 2005;29(12):1652–60.

    Article  PubMed  Google Scholar 

  59. Aukema SM, et al. Double-hit B-cell lymphomas. Blood. 2011;117(8):2319–31.

    Article  CAS  PubMed  Google Scholar 

  60. Wood GS. T-cell receptor and immunoglobulin gene rearrangements in diagnosing skin disease. Arch Dermatol. 2001;137(11):1503–6.

    Article  CAS  PubMed  Google Scholar 

  61. Chiarle R, et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1):11–23.

    Article  CAS  PubMed  Google Scholar 

  62. Stein H, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000;96(12):3681–95.

    CAS  PubMed  Google Scholar 

  63. Beltran B, et al. ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature. J Hematol Oncol. 2009;2:11.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Isimbaldi G, et al. ALK-positive plasmablastic B-cell lymphoma with the Clathrin-ALK gene rearrangement. Pediatr Blood Cancer. 2006;46:390–1.

    Article  PubMed  Google Scholar 

  65. Heisterkamp N, et al. Structural organization of the bcr gene and its role in the Ph’ translocation. Nature. 1985;315(6022):758–61.

    Article  CAS  PubMed  Google Scholar 

  66. Nowell PC, Hungerford DA. Chromosome studies in human leukemia. IV. Myeloproliferative syndrome and other atypical myeloid disorders. J Natl Cancer Inst. 1962;29:911–31.

    CAS  PubMed  Google Scholar 

  67. Rowley JD. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243(5405):290–3.

    Article  CAS  PubMed  Google Scholar 

  68. Baxter EJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054–61.

    Article  CAS  PubMed  Google Scholar 

  69. James C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8.

    Article  CAS  PubMed  Google Scholar 

  70. Kralovics R, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779–90.

    Article  CAS  PubMed  Google Scholar 

  71. Levine RL, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387–97.

    Article  CAS  PubMed  Google Scholar 

  72. Downing JR. The AML1-ETO chimaeric transcription factor in acute myeloid leukaemia: biology and clinical significance. Br J Haematol. 1999;106(2):296–308.

    Article  CAS  PubMed  Google Scholar 

  73. Liu PP, et al. Molecular pathogenesis of the chromosome 16 inversion in the M4Eo subtype of acute myeloid leukemia. Blood. 1995;85(9):2289–302.

    CAS  PubMed  Google Scholar 

  74. Bernardi R, Papa A, Pandolfi PP. Regulation of apoptosis by PML and the PML-NBs. Oncogene. 2008;27(48):6299–312.

    Article  CAS  PubMed  Google Scholar 

  75. Tallman MS, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337(15):1021–8.

    Article  CAS  PubMed  Google Scholar 

  76. Brown P, et al. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood. 2007;110(3):979–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Falini B, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352(3):254–66.

    Article  CAS  PubMed  Google Scholar 

  78. Bienz M, et al. Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clin Cancer Res. 2005;11(4):1416–24.

    Article  CAS  PubMed  Google Scholar 

  79. Kanagal-Shamanna R, et al. Next-generation sequencing-based multi-gene mutation profiling of solid tumors using fine needle aspiration samples: promises and challenges for routine clinical diagnostics. Mod Pathol. 2014;27(2):314–27.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of California at Los Angeles, Los Angeles, CA, USA

    Serge Alexanian M.D.

  2. Kaiser Permanente Medical Center South Sacramento, Sacramento, CA, USA

    Zicheng Mo M.D., Ph.D.

  3. Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Jianyu Rao M.D. (Director of Cytopathology)

Authors
  1. Serge Alexanian M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zicheng Mo M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianyu Rao M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Serge Alexanian M.D. .

Editor information

Editors and Affiliations

  1. Director of Molecular Cytopathology Department of Pathology, The Cleveland Clinic, Cleveland, Ohio, USA

    Bin Yang

  2. Director of Cytopathology Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California, USA

    Jianyu Rao

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Alexanian, S., Mo, Z., Rao, J. (2016). Molecular Biomarkers in Hematopoietic Neoplasms. In: Yang, B., Rao, J. (eds) Molecular Cytopathology. Essentials in Cytopathology, vol 26. Springer, Cham. https://doi.org/10.1007/978-3-319-30741-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-30741-1_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-30739-8

  • Online ISBN: 978-3-319-30741-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation