Chronic myelogenous leukemia pathophysiology

Jump to: navigation, search

Chronic myelogenous leukemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Chronic myelogenous leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Chronic myelogenous leukemia pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Chronic myelogenous leukemia pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Chronic myelogenous leukemia pathophysiology

CDC on Chronic myelogenous leukemia pathophysiology

Chronic myelogenous leukemia pathophysiology in the news

Blogs on Chronic myelogenous leukemia pathophysiology

Directions to Hospitals Treating Chronic myelogenous leukemia

Risk calculators and risk factors for Chronic myelogenous leukemia pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2] Mohamad Alkateb, MBBCh [3] Sima NoorAli, M.D.

Overview

Chronic myeloid leukemia (CML), a myeloproliferative disorder, which is characterized by the uncontrolled expansion of immature bone marrow cells of myeloid origin.The hallmark of CML is the formation of the Philadelphia chromosome resulting from the reciprocal translation (9;22)(q34;q11.2), resulting in a derivative 9q+ and a small 22q- ultimately forms a BCR/ABL fusion gene and production of a BCR/ABL fusion protein. The gene product of the BCR/ABL gene constitutively activates numerous downstream targets including c-myc, Akt and Jun, all of which cause uncontrolled proliferation and survival of CML cells.

Pathogenesis

Genetic Translocation:

Role of reactive oxygen species:

Altered bone marrow pathway signalling:

Role of Integrin:

Blast crisis:

  • Chronic myeloid leukemia (CML) in blast crisis is the transition of CML in chronic or accelerated phase to an acute leukemia.
  • It is characterized by:
  • In light of recent changes in the World Health Organization, definition of acute leukemia, the percentage of blasts required for CML in blastic phase may someday be reduced to 20%.[16]
  • Consistent with the early stem cell nature of CML, blastic transformation may be:
  • Myeloid blast crisis being about two times more common than lymphoid.
Genetic Alterations in Blast crisis:
  • Following genetic changes have been observed which play crucial role in progression of disease phase.
  • Recent studies have implicated activation of the following pathways [21]

Gross Pathology

On gross pathology, no distinctive findings are seen in chronic myeloid leukemia.

Microscopic Pathology

Blast cells are seen on peripheral blood smear of patients of chronic myeloid leukemia which are present during blast crisis.

References

  1. Blank U, Karlsson G, Karlsson S (January 2008). "Signaling pathways governing stem-cell fate". Blood. 111 (2): 492–503. doi:10.1182/blood-2007-07-075168. PMID 17914027.
  2. Wilson A, Trumpp A (February 2006). "Bone-marrow haematopoietic-stem-cell niches". Nat. Rev. Immunol. 6 (2): 93–106. doi:10.1038/nri1779. PMID 16491134.
  3. Blank U, Karlsson G, Karlsson S (January 2008). "Signaling pathways governing stem-cell fate". Blood. 111 (2): 492–503. doi:10.1182/blood-2007-07-075168. PMID 17914027.
  4. Smith C (2003). "Hematopoietic stem cells and hematopoiesis". Cancer Control. 10 (1): 9–16. doi:10.1177/107327480301000103. PMID 12598852.
  5. Chereda B, Melo JV (April 2015). "Natural course and biology of CML". Ann. Hematol. 94 Suppl 2: S107–21. doi:10.1007/s00277-015-2325-z. PMID 25814077.
  6. Blank U, Karlsson G, Karlsson S (January 2008). "Signaling pathways governing stem-cell fate". Blood. 111 (2): 492–503. doi:10.1182/blood-2007-07-075168. PMID 17914027.
  7. Smith C (2003). "Hematopoietic stem cells and hematopoiesis". Cancer Control. 10 (1): 9–16. doi:10.1177/107327480301000103. PMID 12598852.
  8. 8.0 8.1 Thompson PA, Kantarjian HM, Cortes JE (October 2015). "Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015". Mayo Clin. Proc. 90 (10): 1440–54. doi:10.1016/j.mayocp.2015.08.010. PMC 5656269. PMID 26434969.
  9. 9.0 9.1 Jabbour E, Parikh SA, Kantarjian H, Cortes J (October 2011). "Chronic myeloid leukemia: mechanisms of resistance and treatment". Hematol. Oncol. Clin. North Am. 25 (5): 981–95, v. doi:10.1016/j.hoc.2011.09.004. PMC 4428141. PMID 22054730.
  10. Hehlmann R, Hochhaus A, Baccarani M; European LeukemiaNet (2007). "Chronic myeloid leukaemia". Lancet. 370 (9584): 342–50. PMID 17662883.
  11. Jabbour E, Kantarjian H (May 2014). "Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management". Am. J. Hematol. 89 (5): 547–56. doi:10.1002/ajh.23691. PMID 24729196.
  12. Kaleem B, Shahab S, Ahmed N, Shamsi TS (2015). "Chronic Myeloid Leukemia--Prognostic Value of Mutations". Asian Pac. J. Cancer Prev. 16 (17): 7415–23. PMID 26625737.
  13. Antoszewska-Smith J, Pawlowska E, Blasiak J (2017). "Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia". Acta Biochim. Pol. 64 (1): 1–10. doi:10.18388/abp.2016_1396. PMID 27904889.
  14. Toofan P, Wheadon H (October 2016). "Role of the bone morphogenic protein pathway in developmental haemopoiesis and leukaemogenesis". Biochem. Soc. Trans. 44 (5): 1455–1463. doi:10.1042/BST20160104. PMID 27911727.
  15. Verfaillie, Catherine M.; Hurley, Randolph; Zhao, Robert C.H.; Prosper, Felipe; Delforge, Michel; Bhatia, Ravi (1997). "Pathophysiology of CML: Do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone?". Journal of Laboratory and Clinical Medicine. 129 (6): 584–591. doi:10.1016/S0022-2143(97)90192-X. ISSN 0022-2143.
  16. Martin PJ, Najfeld V, Hansen JA, Penfold GK, Jacobson RJ, Fialkow PJ (September 1980). "Involvement of the B-lymphoid system in chronic myelogenous leukaemia". Nature. 287 (5777): 49–50. PMID 6968038.
  17. Salloukh HF, Laneuville P (August 2000). "Increase in mutant frequencies in mice expressing the BCR-ABL activated tyrosine kinase". Leukemia. 14 (8): 1401–4. PMID 10942235.
  18. Kantarjian HM, Keating MJ, Talpaz M, Walters RS, Smith TL, Cork A, McCredie KB, Freireich EJ (September 1987). "Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients". Am. J. Med. 83 (3): 445–54. PMID 3477958.
  19. Ahuja, H.; Bar-Eli, M.; Advani, S. H.; Benchimol, S.; Cline, M. J. (1989). "Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia". Proceedings of the National Academy of Sciences. 86 (17): 6783–6787. doi:10.1073/pnas.86.17.6783. ISSN 0027-8424.
  20. Hasford J, Pfirrmann M, Hehlmann R, Baccarani M, Guilhot F, Mahon FX, Kluin-Nelemans HC, Ohnishi K, Thaler J, Steegmann JL (January 2003). "Prognosis and prognostic factors for patients with chronic myeloid leukemia: nontransplant therapy". Semin. Hematol. 40 (1): 4–12. doi:10.1053/shem.2003.50006. PMID 12563607.
  21. Donato, N. J. (2003). "BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571". Blood. 101 (2): 690–698. doi:10.1182/blood.V101.2.690. ISSN 0006-4971.
  22. Center for Disease Control and Prevention. Public Health Image Library 2015.http://phil.cdc.gov/phil/details_linked.asp?pid=6

Linked-in.jpg