Leukemia

From Dog
Acute lymphoblastic leukemia in a dog, showing numerous lymphoblasts[1]
A rapidly emerging rectal chloroma in association with monocytic leukemia in a dog[2]

Acute myeloid leukemia in dogs is a neoplastic disorder of dogs defined as elevated levels of circulating immature leucocytes (lymphoblasts).

In most dogs, it is recognized as a primary hematological variant of canine lymphoma.

This condition may occur as a primary disease or secondary to other causes (e.g. histiocytic sarcoma) and may involve all leucocytes or a particular subset.

Although the cause of primary leukemia in dogs is unknown, the pathogenesis appears to involve critical hematological components, particularly leukemia initiating cells which develop as a result of age-related and breed-predisposed genetic mutations in hematopoietic stem cell lines[3] that overwhelm the pituitary production of leukemia inhibitory factor[4][5]. These leukemia initiating cells consequently invoke changes in matrix metalloproteinases and vascular endothelial growth factors which cause most of the hemodynamic features of the disease[6].

The forms of leukemia reported in dogs include:

  • Basophilic leukemia
  • Dendritic cell leukemia[7]
  • Eosinophilic leukemia - to be differentiated from hypereosinophilic syndrome
  • Erythroid leukemia - characterized by pancytopenia[8]
  • Intravascular lymphoma (NK cell origin) with overt leukemia[9]
  • Lymphocytic leukemia
- B-cell lymphocytic leukemia-lymphoma complex[10][11]
- T-cell lymphocytic leukemia[12] - anemia, neutropenia and thrombocytopenia[13] - predispositon in the Golden Retriever[14]
- characterized by megakaryocytosis, with neoplastic megakaryoblasts can be identified in spleen, liver, mesenteric lymph nodes and pulmonary vasculature[17]

Affected dogs usually present with lethargy, mental depression, fever, proteinuria and anorexia. Other less frequent symptoms may be observed such as nystagmus and ataxia.

Blood tests often reveal varying degrees of non-regenerative anemia and leucocytosis, but unusual cases may present with subset disorders such as monocytosis, lymphopenia, neutropenia or thrombocytopenia. Other symptoms include lymphadenopathy and splenomegaly[24].

Rarely, skin involvement may be the first manifestation of acute leukemia, in which the bone marrow biopsy shows a precursor lesion (myeloproliferative or myelodysplastic syndrome) or normal findings[25]. Rare forms of secondary disease include granulocytic sarcoma[26].

A presumptive diagnosis can be established based on clinical findings, hematological analysis of blood samples and thoracic and abdominal radiographs (to exclude tumors) and biopsies of bone marrow tissue.

Definitive diagnosis requires histopathological examination of bone marrow samples, immunohistochemical analysis (using CD61 and von Willebrand factor)[27][28], PCR testing for detection of the NK cell[29] and bcr-abl fusion gene[30] mutations.

A differential diagnosis would include other causes of leucocytosis including myelodysplasia syndrome and myeloproliferative neoplasms (e.g. polycythemia vera[31], multiple myeloma, hemangiosarcoma and lymphoma)

Whole blood transfusion may be required in severely anemia patients and chemotherapy is recommended in most cases.

Numerous regimens of drugs is usually recommended as resistance to many combinations have been reported. Various chemotherapy combinations include:

The prognosis in many cases in dogs is guarded, particularly in younger dogs[34] since many are detected at advanced stages.

References

  1. Vetnext
  2. Thakar MS et al (2009) Transmission and expansion of HOXB4-induced leukemia in two immunosuppressed dogs: implications for a new canine leukemia model. Exp Hematol 37(10):1157-1166
  3. Bonnet D & Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737
  4. Schäfer-Somi S et al (2009) Uterine progesterone receptor and leukaemia inhibitory factor mRNA expression in canine pregnancy. Reprod Domest Anim 44(2):109-114
  5. Hanson JM et al (2010) Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor in the canine pituitary gland and corticotrope adenomas. Domest Anim Endocrinol 38(4):260-271
  6. Aricò A et al (2012) Matrix metalloproteinases and vascular endothelial growth factor expression in canine leukaemias. Vet J Nov 7
  7. Allison RW et al (2008) Dendritic cell leukemia in a Golden Retriever. Vet Clin Pathol 37(2):190-197
  8. Mylonakis ME et al (2012) Presumptive pure erythroid leukemia in a dog. J Vet Diagn Invest 24(5):1004-1007
  9. Lane LV et al (2012) Canine intravascular lymphoma with overt leukemia. Vet Clin Pathol 41(1):84-91
  10. Kol A et al (2012) B-cell lymphoma with plasmacytoid differentiation, atypical cytoplasmic inclusions, and secondary leukemia in a dog. Vet Clin Pathol Dec 3
  11. Statham-Ringen KA et al (2012) Evaluation of a B-cell leukemia-lymphoma 2-specific radiolabeled peptide nucleic acid-peptide conjugate for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma. Am J Vet Res 73(5):681-688
  12. Okawa T et al (2012) Development of high-grade B-cell lymphoma concurrent with T-cell chronic lymphocytic leukemia in a dog. J Vet Med Sci 74(5):677-680
  13. Williams MJ et al (2008) What is your diagnosis? Pancytopenia in a dog. Vet Clin Pathol 37(4):429-433
  14. Maruo T et al (2009) Large granular lymphocytic leukaemia complicated with histiocytic sarcoma in a dog. J S Afr Vet Assoc 80(4):261-263
  15. Hikasa Y et al (2000) Connective tissue-type mast cell leukemia in a dog. J Vet Med Sci 62(2):187-190
  16. Barger AM et al (2012) Cytologic identification of erythrophagocytic neoplasms in dogs. Vet Clin Pathol 41(4):587-589
  17. Ameri M et al (2010) Acute megakaryoblastic leukemia in a German Shepherd dog. Vet Clin Pathol 39(1):39-45
  18. Amati M et al (2012) Carcinocythaemia (carcinoma cell leukaemia) in a dog: an acute leukaemia-like picture due to metastatic carcinoma. J Small Anim Pract 53(8):476-479
  19. Cruz Cardona JA et al (2011) BCR-ABL translocation in a dog with chronic monocytic leukemia. Vet Clin Pathol 40(1):40-47
  20. Rossi G et al (2009) Extreme monocytosis in a dog with chronic monocytic leukaemia. Vet Rec 165(2):54-56
  21. Tasca S et al (2010) High serum and urine lysozyme levels in a dog with acute myeloid leukemia. J Vet Diagn Invest 22(1):111-115
  22. Figueiredo JF et al (2012) Acute myeloblastic leukemia with associated BCR-ABL translocation in a dog. Vet Clin Pathol 41(3):362-368
  23. Tomiyasu H et al (2011) Spontaneous acute erythroblastic leukaemia (AML-M6Er) in a dog. J Small Anim Pract 52(8):445-447
  24. Comazzi S et al (2010) Acute megakaryoblastic leukemia in dogs: a report of three cases and review of the literature. J Am Anim Hosp Assoc 46(5):327-335
  25. Aguilera SB et al (2010) Leukemia cutis in a patient with acute myelogenous leukemia: A case report and review of the literature. Cutis 85:31–36
  26. Mayr B et al (1999) Cytogenetic, ras, and p53: studies in cases of canine neoplasms (hemangiopericytoma, mastocytoma, histiocytoma, chloroma). J Hered 90(1):124-128
  27. Ferreira HM et al (2011) Myeloperoxidase-positive acute megakaryoblastic leukemia in a dog. Vet Clin Pathol 40(4):530-537
  28. Valentini F et al (2012) Use of CD9 and CD61 for the characterization of AML-M7 by flow cytometry in a dog. Vet Comp Oncol 10(4):312-318
  29. Usher SG et al (2009) RAS, FLT3, and C-KIT mutations in immunophenotyped canine leukemias. Exp Hematol 37(1):65-77
  30. Avery A (2009) Molecular diagnostics of hematologic malignancies. Top Companion Anim Med 24(3):144-150
  31. Juopperi TA et al (2011) Prognostic markers for myeloid neoplasms: a comparative review of the literature and goals for future investigation. Vet Pathol 48(1):182-197
  32. Kim JH et al (2012) Combined treatment of 3-hydroxyflavone and imatinib mesylate increases apoptotic cell death of imatinib mesylate-resistant leukemia cells. Leuk Res 36(9):1157-1164
  33. Willmann M et al (2009) Chemotherapy in canine acute megakaryoblastic leukemia: a case report and review of the literature. In Vivo 23(6):911-918
  34. Comazzi S et al (2011) Immunophenotype predicts survival time in dogs with chronic lymphocytic leukemia. J Vet Intern Med 25(1):100-106