SR Cole

The c-kit proto-oncogene encodes a 145- to 160-Kd transmembrane tyrosine kinase, which is a member of the platelet-derived growth factor receptor family and is allelic with the murine white spotting locus (W). W mutations affect several aspects of hematopoiesis, most notably erythroid progenitors and mast cells. A monoclonal antibody, YB5.B8, had been raised against the leukemic blasts of a patient with M1-type acute myelocytic leukemia (AML) and it precipitates a 150-Kd cell surface glycoprotein from leukemic cells. The YB5.B8 epitope is expressed on mast cells, on up to 3% of normal mononuclear bone marrow cells, and it identifies a sub-group of AML patients with a poor prognosis. In view of similarities noted between the cell surface antigen identified by YB5.B8 and the c-kit protein product, we performed experiments to determine whether they are identical. c-kit RNA expression in the cell lines HEL (human erythroleukemia) and A172 (glioblastoma) was shown to parallel the expression of the YB5.B8 epitope in these lines as measured by flow cytometry. Immunoprecipitation analysis with anti-kit serum and YB5.B8 antibody indicated that the two antibodies identified proteins of identical size in HEL (155 Kd) and A172 (145 Kd) cells, and sequential immunoprecipitations with the kit and the YB5.B8 antibodies demonstrated that the two antibodies recognize the same molecule. The proteins identified by both the anti-kit and YB5.B8 antibodies displayed in vitro autophosphorylation activity in immune complex kinase assays. In addition, YB5.B8 was able to inhibit the binding of the kit ligand to HEL cells. These studies provide evidence that the YB5.B8 antigen and the c-kit protein product are identical and raise certain hypotheses regarding the role of c-kit in AML.

Allopatric populations of the pseudomyine rodents Pseudomys albocinereus, P. delicatulus, the P. nanus-P. gracilicaudatus complex, Zyzomys argurus and Mesembriomys gouldi were surveyed for electrophoretic variability of 14-17 red cell and plasma proteins. Few or no electrophoretic differences were found to parallel the chromosomal differences between populations of P. delicatulus, Z. argurus, and M. gouldi. Populations of the P. nanus-P. gracilicaudatus complex, however, fell into two groups defined both chromosomally and electrophoretically. The western form (P. nanus) extends from Western Australia into the Northern Territory whilst the eastern form (P. gracilicaudatus) occurs only along the east coast of Queensland and New South Wales. The biochemical differentiation between South Australian, Western Australian mainland and Bernier Island P. albocinereus parallels the chromosomal, morphological and breeding data, all of which indicate that the Western Australian mainland and Bernier Island forms belong to one species (P. albocinereus), whilst the South Australian form represents a distinct biological species (P. apodemoides).

A total of 168 specimens of 38 species of Australian native murid rodents and three species of nonnative rodents were screened electrophoretically at 20 loci. Genetic and phylogenetic relationships among species were assessed by means of Average Linkage Cluster and Wagner Analysis respectively. The major conclusions of the analysis are: the genera Melomys, Leggadina, Zyzomys, Notomys and Rattus ire each monophyletic, at least for the species we had; the genus Pseudomys is largely monophyletic; although it may be paraphyletic with respect to Mastacomys and Leporillus; the genus Pseudomys is nevertheless a genetically diverse group consisting of at least four groups, none of which correspond to the earlier genera Gyomys and Thetomys; the 'Old Endemics', the water rats, and the Uromys- Melomys groups are genetically more similar to each other than any is to Rattus. Within Rattus, the following groupings emerge: R. sordidus, R. colletti and R. villosissimus: R. t. tunneyi and R. t. culmorum; R. l. leucopus and R. l. cooktownensis; R. fuscipes coracius, R. f: assimilis and R. f. greyii.

The c-kit proto-oncogene encodes a 145- to 160-Kd transmembrane tyrosine kinase, which is a member of the platelet-derived growth factor receptor family and is allelic with the murine white spotting locus (W). W mutations affect several aspects of hematopoiesis, most notably erythroid progenitors and mast cells. A monoclonal antibody, YB5.B8, had been raised against the leukemic blasts of a patient with M1-type acute myelocytic leukemia (AML) and it precipitates a 150-Kd cell surface glycoprotein from leukemic cells. The YB5.B8 epitope is expressed on mast cells, on up to 3% of normal mononuclear bone marrow cells, and it identifies a sub-group of AML patients with a poor prognosis. In view of similarities noted between the cell surface antigen identified by YB5.B8 and the c-kit protein product, we performed experiments to determine whether they are identical. c-kit RNA expression in the cell lines HEL (human erythroleukemia) and A172 (glioblastoma) was shown to parallel the expression of the YB5.B8 epitope in these lines as measured by flow cytometry. Immunoprecipitation analysis with anti-kit serum and YB5.B8 antibody indicated that the two antibodies identified proteins of identical size in HEL (155 Kd) and A172 (145 Kd) cells, and sequential immunoprecipitations with the kit and the YB5.B8 antibodies demonstrated that the two antibodies recognize the same molecule. The proteins identified by both the anti-kit and YB5.B8 antibodies displayed in vitro autophosphorylation activity in immune complex kinase assays. In addition, YB5.B8 was able to inhibit the binding of the kit ligand to HEL cells. These studies provide evidence that the YB5.B8 antigen and the c-kit protein product are identical and raise certain hypotheses regarding the role of c-kit in AML.