AML: immunophenotypic heterogeneity and prognostic significance of c-kit expression.
Antigenic profiles in AML that have generally accepted prognostic significance, and allow treatment stratification, have not yet been defined. In a previous report of Ashman et al., the proto-oncogene c-kit defined by binding of the moab YB5.B8 was expressed on about one third of AML cases, mainly of the undifferentiated FAB-subtypes and associated with poor prognosis and overall survival. In this study, the moab 17F11 also directed against the c-kit structure stained 41/47 AML and 6/8 CML blast specimens, whereas all investigated 40 ALL samples were c-kit negative. c-kit was not restricted to any particular, undifferentiated FAB-subtype, but found in 9/9 AML-M0/M1, 18/19 AML-M2, 0/1 AML-M3, 11/13 AML-M4 and 3/5 AML-M5 subtypes. Immunophenotypical analysis showed no restriction of c-kit expression to immature, CD34+ precursors, but c-kit was also expressed on CD4+ CD34- precursor cells differentiating towards the monocyte lineage. In addition, multi-color labelings revealed an extraordinary heterogeneity of concomitant antigen expression on c-kit+ cells 10/36 c-kit+ CD34+ samples expressing CD56 and 16/36 c-kit+ CD34+ samples being CD7 positive; two c-kit+ CD34+ specimens carried the B-cell antigen CD19. In correlation to clinical outcome c-kit expression as single parameter was not predictive for poor response to therapy and short survival as previously suggested.
Reuss-Borst
M A
MA
Second Department of Internal Medicine, Medical University Clinic, Tübingen, Germany.
Bühring
H J
HJ
Schmidt
H
H
Müller
C A
CA
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics*; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases