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               Lymphoid Leukemias, Myeloid Neoplasia, and Myelodysplastic Syndrome
               Angela R. Kozicki, DVM, DACVIM (Oncology)

               Bluepearl Veterinary Partners, Southfield, MI, USA



                 Lymphoid Leukemias                               and flow cytometry in which cell suspensions are stained
                                                                  with specific fluorochromes, analyzed by a focused laser
               Etiology/Pathophysiology                           beam and sorted  by  size and DNA content (ploidy of
                                                                  cells). Immunophenotyping can identify the presence of
               Lymphoid leukemias are differentiated as either chronic   different blood cell lineages but cannot predict clonality
               lymphocytic leukemia (CLL) or acute lymphoblastic leu­  (whether a population arises from a single cell).
               kemia (ALL). CLL is a clonal, neoplastic proliferation of   It is important to know normal percentages of lym­
               small, mature‐looking lymphocytes that manifests as a   phocyte subsets found in the peripheral blood of dogs
               persistent, often severe lymphocytosis. Three subsets   and cats to be able to distinguish a benign or reactive
               have been recognized based on immunophenotyping.   process from a malignant one. In general, peripheral
               The most common is granular T‐CLL which consists of   lymphocytes of dogs consist of ~80% T cells (CD3+ or
               proliferations of cytotoxic (CD8+) T cells. Despite con­  CD5+) with 45% being helper T cells (CD4+), 25% being
               ventional thinking that CLL is always a primary bone   cytotoxic T cells (CD8+) and the remainder being dou­
               marrow disease, granular T‐CLL is considered a primary   ble‐negative T cells (CD4‐, CD8‐). Approximately 15%
               splenic disease which can be verified by expression of a   are B lymphocytes (CD21+) and the remaining lympho­
               marker for splenic red pulp (CD11d). The second is B‐  cytes are natural killer (NK) cells. Cats are very similar
               CLL  (CD21+,  CD79a+)  and  the  third  is  nongranular/  but have slightly fewer T cells (~75%) and a greater per­
               atypical T‐CLL (CD3+) in which no consistent pattern of   centage of B cells (~25%) in the peripheral blood.
               concurrent CD4 or CD8 expression is found. ALL is    The etiology of lymphoid leukemias is largely
               defined by proliferation of immature lymphoblasts in the   unknown. In people, there is no known association with
               bone marrow or peripheral blood. The immunopheno­  radiation,  chemicals  or  alkylating  agents  and  no  viral
               type of ALL is typically B cell (CD21+, CD3‐, CD4‐,   cause. Genetic factors are suspected in both humans and
               CD8‐) with an acute, immature lineage based on expres­  dogs but immunophenotype of the neoplastic cells in
               sion of CD34, a stem cell marker.                  these species is different in that most human lymphoid
                 Classification of lymphocytes involves assessment of   leukemias are B cell in origin. Therefore, it is unwise to
               cell surface antigen (marker) expression that pertains to   try to make direct correlations between species since dif­
               both lineage and function. This classification is usually   ferent causative factors may be involved. In cats, retrovi­
               performed by immunophenotyping. Immunophenotyping   ruses such as feline leukemia virus (FeLV) play a role
               consists of the application of   antibodies specific for dif­  since ~60–80% of cats with ALL are FeLV+. There is no
               ferentiation antigens of lymphocytes and other immune   known association between FeLV and CLL in cats and no
               cells to identify lineages of these cells present in neoplas­  evidence of a retroviral cause in dogs.
               tic or reactive diseases. Immunophenotyping can be per­
               formed on cytology smears, blood smears, fluids (blood
               or bone marrow), formalin‐fixed paraffin sections or   Epidemiology
               snap‐frozen tissue sections. Immunophenotyping tests   In people, CLL is an indolent disease of older adults (>60
               include immunohistochemistry (on tissue samples),   years of age) and accounts for 25–30% of all adult leuke­
               immunocytochemistry (on cytologic or fluid samples),   mias among white populations in North America and


               Clinical Small Animal Internal Medicine Volume II, First Edition. Edited by David S. Bruyette.
               © 2020 John Wiley & Sons, Inc. Published 2020 by John Wiley & Sons, Inc.
               Companion website: www.wiley.com/go/bruyette/clinical
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