Chronic Granulocytic Leukemia Complicated by Ulcerative Colitis: Elevated Leukocyte Alkaline Phosphatase and Possible Modifier Gene Deletion.

EUKOCYTE ALKALINE PHOSPHATASE ( LAP) determinations have proved of clinical value in the differential diagnosis of certain myeloproliferative disorders. Low or absent enzyme activity of mature neutrophils is characteristic of chronic granulocytic leukemia, in contradistinction to the usual high levels in polycythemia vera and myelofibrosis with myeloid metaplasia.13 There are also a number of other conditions in which LAP may be abnormal, one of the more notable, from a theoretical standpoint, being the elevation lately demonstrated in mongolism.47 Although the significance of such deviations remains obscure recent cytogenetic findings have fostered considerable speculation about the control of LAP production. In this regard the small acrocentric chromosome 21 has occupied a central position following the discoveries of its triplication (trisomy) in mongolism8 and diminution (Philadelphia or Ph’ chromosome) in chronic granulocytic leukemia.9 From correlations between these and the respective LAP abnormalities has emerged the hypothesis4’5 that the phosphatase deficiency in chronic granulocytic leukemia may be the result of loss (presumably by deletion) from chromosome 21 of a segment containing the gene(s) responsible for LAP synthesis. Conversely, in mongolism the heightened LAP activity could be attributable to the supernumerary chromosome 21 and a surfeit of functioning genes. However, a simple gene-dose interpretation of this nature cannot easily be reconciled with some pertinent facts, as has been ably underscored by King and her co-workers.#{176} In the following report of chronic granulocytic leukemia in a boy with concurrent ulcerative colitis, LAP was greatly elevated in spite of the presence in his bone marrow of the typical minute Ph1 chromosome. Only after the colitis entered a quiescent phase did the initial enzyme activity decline to the low levels compatible with chronic granulocytic leukemia. This lability of LAP offers additional evidence against the view that loss of a structural gene from chromosome 21 is the basis for the diminished alkaline phosphatase content of neutrophils in chronic granulocytic leukemia.