Chronic lymphocytic leukemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shalinder Singh, M.B.B.S.[2] Haytham Allaham, M.D. [3]

Overview

Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulin production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis, characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleolus, and the presence of smudge cells.

Pathogenesis

The pathogenesis of Chronic lymphocytic leukemia can be described as following:

Immunology

Cytogenetics

  • Chromosome 11 long arm deletion (11q22-q23): Relapsing disease, refractory to initial therapy, poor prognosis, large-scale lymph node involvement and shorter survival[10][11]
  • Chromosome 13 long arm deletion (most common genetic mutation): Better prognosis[12]
  • Chromosome 17p13 deletion: Tumor suppressor gene TP53 deletion, relapsing disease and refractory to initial therapy[12][13]
  • Trisomy 12 : Increased proliferation and advanced disease.[14]

Molecular Genetics

  • Somatic genetic mutations and associated factors involved in the pathogenesis of chronic lymphocytic leukemia include:
  • The type of the genetic mutation is considered one of the important factors that determine the optimal management protocol of chronic lymphocytic leukemia patients.

Microscopic Pathology

  • Illustrated below is a series of microscopic images observed in chronic lymphocytic leukemia:

References

  1. Herishanu Y, Katz BZ, Lipsky A, Wiestner A (April 2013). "Biology of chronic lymphocytic leukemia in different microenvironments: clinical and therapeutic implications". Hematol. Oncol. Clin. North Am. 27 (2): 173–206. doi:10.1016/j.hoc.2013.01.002. PMID 23561469.
  2. Herishanu Y, Katz BZ, Lipsky A, Wiestner A (April 2013). "Biology of chronic lymphocytic leukemia in different microenvironments: clinical and therapeutic implications". Hematol. Oncol. Clin. North Am. 27 (2): 173–206. doi:10.1016/j.hoc.2013.01.002. PMID 23561469.
  3. Strati P, Shanafelt TD (July 2015). "Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification". Blood. 126 (4): 454–62. doi:10.1182/blood-2015-02-585059. PMID 26065657.
  4. Jain P, O'Brien S (December 2012). "Richter's transformation in chronic lymphocytic leukemia". Oncology (Williston Park, N.Y.). 26 (12): 1146–52. PMID 23413591.
  5. Jain P, O'Brien S (December 2012). "Richter's transformation in chronic lymphocytic leukemia". Oncology (Williston Park, N.Y.). 26 (12): 1146–52. PMID 23413591.
  6. Fournier S, Delespesse G, Rubio M, Biron G, Sarfati M (April 1992). "CD23 antigen regulation and signaling in chronic lymphocytic leukemia". J. Clin. Invest. 89 (4): 1312–21. doi:10.1172/JCI115717. PMC 442993. PMID 1532590.
  7. Geisler CH, Larsen JK, Hansen NE, Hansen MM, Christensen BE, Lund B, Nielsen H, Plesner T, Thorling K, Andersen E (October 1991). "Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia". Blood. 78 (7): 1795–802. PMID 1717071.
  8. Friedman DR, Guadalupe E, Volkheimer A, Moore JO, Weinberg JB (December 2018). "Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B-cell receptor signalling". Br. J. Haematol. 183 (5): 747–754. doi:10.1111/bjh.15632. PMID 30407619.
  9. Haerzschel A, Catusse J, Hutterer E, Paunovic M, Zirlik K, Eibel H, Krenn PW, Hartmann TN, Burger M (December 2016). "BCR and chemokine responses upon anti-IgM and anti-IgD stimulation in chronic lymphocytic leukaemia". Ann. Hematol. 95 (12): 1979–1988. doi:10.1007/s00277-016-2788-6. PMC 5093209. PMID 27542958.
  10. Döhner H, Stilgenbauer S, James MR, Benner A, Weilguni T, Bentz M, Fischer K, Hunstein W, Lichter P (April 1997). "11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis". Blood. 89 (7): 2516–22. PMID 9116297.
  11. Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M, Lichter P (December 2000). "Genomic aberrations and survival in chronic lymphocytic leukemia". N. Engl. J. Med. 343 (26): 1910–6. doi:10.1056/NEJM200012283432602. PMID 11136261.
  12. 12.0 12.1 Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M, Lichter P (December 2000). "Genomic aberrations and survival in chronic lymphocytic leukemia". N. Engl. J. Med. 343 (26): 1910–6. doi:10.1056/NEJM200012283432602. PMID 11136261.
  13. Guièze R, Robbe P, Clifford R, de Guibert S, Pereira B, Timbs A, Dilhuydy MS, Cabes M, Ysebaert L, Burns A, Nguyen-Khac F, Davi F, Véronèse L, Combes P, Le Garff-Tavernier M, Leblond V, Merle-Béral H, Alsolami R, Hamblin A, Mason J, Pettitt A, Hillmen P, Taylor J, Knight SJ, Tournilhac O, Schuh A (October 2015). "Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL". Blood. 126 (18): 2110–7. doi:10.1182/blood-2015-05-647578. PMID 26316624.
  14. Garcìa-Marco JA, Price CM, Ellis J, Morey M, Matutes E, Lens D, Colman S, Catovsky D (November 1996). "Correlation of trisomy 12 with proliferating cells by combined immunocytochemistry and fluorescence in situ hybridization in chronic lymphocytic leukemia". Leukemia. 10 (11): 1705–11. PMID 8892671.
  15. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L, Zhang W, Vartanov AR, Fernandes SM, Goldstein NR, Folco EG, Cibulskis K, Tesar B, Sievers QL, Shefler E, Gabriel S, Hacohen N, Reed R, Meyerson M, Golub TR, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ (December 2011). "SF3B1 and other novel cancer genes in chronic lymphocytic leukemia". N. Engl. J. Med. 365 (26): 2497–506. doi:10.1056/NEJMoa1109016. PMC 3685413. PMID 22150006.
  16. Oscier DG, Rose-Zerilli MJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, Parker H, Parker A, Gardiner A, Collins A, Else M, Cross NC, Catovsky D, Strefford JC (January 2013). "The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial". Blood. 121 (3): 468–75. doi:10.1182/blood-2012-05-429282. PMID 23086750.
  17. Woyach JA, Johnson AJ, Byrd JC (August 2012). "The B-cell receptor signaling pathway as a therapeutic target in CLL". Blood. 120 (6): 1175–84. doi:10.1182/blood-2012-02-362624. PMID 22715122.
  18. Oscier DG, Rose-Zerilli MJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, Parker H, Parker A, Gardiner A, Collins A, Else M, Cross NC, Catovsky D, Strefford JC (January 2013). "The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial". Blood. 121 (3): 468–75. doi:10.1182/blood-2012-05-429282. PMID 23086750.
  19. 19.0 19.1 19.2 19.3 Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015

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