Because mutations in receptor tyrosine kinases may contribute to cellular transformation, studies were undertaken to examine c-kit in human leukemia. Isoforms of c-kit have been characterized in the human megakaryoblastic leukemia cell line M-07. Deletion of the four amino acids Gly-Asn-Asn-Lys in the extracellular domain represents an alternatively spliced isoform that has been shown by others, in mice, to be associated with constitutive receptor autophosphorylation (Reith et al, EMBO J 10:2451, 1991). Additional isoforms differ in the inclusion or exclusion of a serine residue in the interkinase domain, a region that contains the binding site for phosphatidylinositol 3- kinase. By RNase protection analysis, we have shown coexpression of the Gly-Asn-Asn-Lys+ and Gly-Asn-Asn-Lys- isoforms, with dominance of the Gly-Asn-Asn-Lys- transcript, in normal human bone marrow, normal melanocytes, a range of tumor cell lines, and the blasts of 23 patients with acute myeloid leukemia. Analysis of transcripts for the Ser+ and Ser- isoforms also showed coexpression in all normal and leukemic cells examined. The ratios of isoform expression for both the Gly-Asn-Asn-Lys and Ser variants were relatively constant, providing no evidence in the tumors examined that upregulation of one isoform contributes to the neoplastic process.

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An approximate stress intensity factor is derived for an embedded elliptical crack in a plate which is subjected to uniaxial tension in the direction perpendicular to the crack surface. The major axis of an eccentrically located elliptical crack is assumed to be parallel with the two plate surfaces. The approximate stress intensity factors on the minor axis of the elliptical crack are then determined as at3o\/a\h where a is a correction factor due to the curvature of the ellipse and 5 is a correction factor due to the eccentricity of the crack in rhe wall.

The influence of specimen design on plane strain fracture toughness (KIc) was studied by fracturing 2219-T87 aluminum and 5Al-2.5Sn ELI titanium alloy single-edge notched bend (SENB), single-edge notched tension (SENT), compact tension (CT), and surface flawed (SF) specimens at 72 F (295 K) in laboratory air, at -320 F (78 K) in liquid nitrogen, and at -423 F (20 K) in liquid hydrogen. Specimen thickness for all SENB, SENT, and CT specimens except titanium/room air specimens was approximately 2.5(KIc/σys)2 in. Specimen thickness for SF specimens ranged from 2.5(KIc/σys)2 to 0.25(KIc/σys)2. Relative orientations of crack propagation and rolling directions were identical in all specimens of a given alloy. For aluminum alloy specimens having thicknesses of 2.5(KIc/σys)2, SENB, SENT, and SF specimen tests yielded consistent fracture toughness values at all test temperatures whereas CT specimen tests always yielded lower fracture toughness. For titanium alloy specimens having thicknesses of 2.5(KIc/σys)2, SENB, SENT, CT, and SF specimen tests yielded consistent fracture toughness values at -423 F (20 K); at -320 F (78 K), fracture toughness values from SF specimen tests were significantly greater than those obtained from tests of other specimen types; at 72 F (295 K) no valid fracture toughness data were obtained. Both aluminum alloy SF specimen tests yielded consistent fracture toughness (KIE) values when both flaw depth and distance between flaw tip and back specimen face exceeded 0.5(KIE/σys)2.

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