Page 756 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

734 PART IV Specific Malignancies in the Small Animal Patient

TABLE 33.13 Subtypes of Leukemias and Dysplasias the JAK2, CALR, and MPL genes have been identified in people
Adapting the FAB System with polycythemia vera (PV), essential thrombocythemia (ET),
680
and primary myelofibrosis.
Only JAK2 mutations have been
VetBooks.ir Subtype Description investigated in dogs with PV, and an identical mutation to that
Myelofibrosis
681
in people was found in 1 of 5 cases in dogs.
Acute Leukemias
AUL Acute undifferentiated leukemia (formerly called is considered a response to injury and may occur secondary
to other neoplasms, systemic inflammation, drug exposure, or
reticuloendotheliosis)
FeLV infection in cats.
M1 Myeloblastic leukemia, without differentiation
M2 Myeloblastic leukemia, with some neutrophilic
differentiation Polycythemia Vera
M3 Promyelocytic leukemia (not recognized in animals) Polycythemia vera (PV) is a clonal disorder of stem cells,
M4 Myelomonocytic leukemia although whether the defect is in the pluripotent stem cell
or the hematopoietic multipotent stem cell is still not clear.
M5a Monocytic leukemia, without differentiation The disease is rare and must be distinguished from more com-
M5b Monocytic leukemia, with some monocytic dif- mon causes of polycythemia. In PV, there is neoplastic pro-
ferentiation liferation of the erythroid series with terminal differentiation
to RBCs. The disease has been reported in dogs that tend to
M6 Erythroleukemia
be middle-aged with no breed or sex predilection 682–692 and
M6Er Variant of M6 with erythroblasts comprising ery- is characterized by an increased RBC mass evidenced by an
throid component increased packed cell volume (PCV), RBC count, and hemo-
globin concentration. The PCV is typically in the range of
M7 Megakaryoblastic leukemia
65% to 85%. The bone marrow is hyperplastic, although the
Chronic Myeloid Leukemias myeloid-to-erythroid (M:E) ratio tends to be normal. In con-
CML Chronic myelogenous leukemia trast to the disease in humans, other cell lines do not appear
to be involved and transformation to other MPNs has not
CMML Chronic myelomonocytic leukemia
been reported. The disease in dogs may be more appropriately
CMoL Chronic monocytic leukemia termed primary erythrocytosis. In humans, progenitor cells
have an increased sensitivity to insulin-like growth factor 1,
Hematopoietic Dysplasia
which stimulates hematopoiesis. 691 It is not known whether
MDS Myelodysplastic syndrome this hypersensitivity is the primary defect or is secondary to
another gene mutation. In any case, the result is overproduc-
MDS-Er Myelodysplastic syndrome with erythroid predomi- tion of red blood cells (RBCs). Acquired JAK2 gene mutations
nance
are identified in 90% of humans with PV, and an identi-
cal mutation in the JAK2 gene of 1 of 5 dogs with PV was
reported. 681

Chronic Myelogenous Leukemia

what has been found for human AML. 678 BCR–ABL transloca- In dogs, CML is more similar to chronic neutrophilic leuke-
tion is also reported in dogs with acute myeloblastic leukemia. 679 mia, a rare form of MPN in humans, than to CML in humans
Recurrent DNA copy number abnormalities (CNA) have been because it is a neoplastic proliferation of the neutrophil series,
interrogated in 24 dogs with AML and there is potential for CNA although concurrent eosinophilic and basophilic differen-
clustering to be used in diagnostic models. 626 In addition to serv- tiation can occur. CML can occur in dogs of any age. 693–698
ing as diagnostic and prognostic markers, cytogenetic lesions may Neutrophils and neutrophilic precursors accumulate in bone
be therapeutic targets. As cytogenetic abnormalities continue to marrow and peripheral blood as well as in other organs. The
be identified, this information will need to be incorporated into peripheral WBC count is usually, but not always, greater than
classification schemes. 100,000/μL. Both immature and mature neutrophils are pres-
ent (see Fig. 33.21F). Mature forms are usually more numer-
Myeloproliferative Neoplasms ous, but sometimes an “uneven” left shift is present. Signs of
dysplasia may be evident, including hypersegmentation, ringed
Myeloproliferative neoplasms (MPNs), previously termed nuclei, and giant forms. Eosinophils and basophils may also be
chronic myeloproliferative disorders, are characterized by exces- increased. The bone marrow is characterized by granulocytic
sive production of differentiated bone marrow cells, result- hyperplasia and morphologic abnormalities may not be present.
ing in the accumulation of erythrocytes (polycythemia vera), Erythroid and megakaryocytic lines may be affected, resulting
granulocytes and/or monocytes (CML and its variants), or in anemia, thrombocytopenia, or less commonly, thrombocyto-
platelets (essential thrombocythemia). Primary myelofibrosis, sis. This disorder must be distinguished from severe or extreme
a clonal disorder of bone marrow stromal cells characterized neutrophilic leukocytosis (“leukemoid reactions”) caused by
by proliferation of megakaryocytes and granulocytic precursors inflammation or immune-mediated diseases. Extreme neutro-
with accumulation of collagen in bone marrow, has been rec- philia can also occur as a paraneoplastic syndrome. In humans
ognized only rarely in animals. Phenotypic-driver mutations in with CML, characteristic cytogenetic abnormalities are present