Leukocyte Alkaline Phosphatase (LAP)

Historically, the diagnostic utility of leukocyte alkaline phosphatase (LAP) activity (measured as the LAP score) was in the differential diagnosis of leukocytosis (Leukocyte Alkaline Phosphatase in Hematology 4th ed. McGraw-Hill: New York 1990). The LAP score was usually low in chronic myeloid leukemia (CML), which helped distinguish CML from other myeloproliferative neoplasms with leukocytosis and inflammatory leukemoid reactions, both of which had a normal or increased LAP score. Additionally, it was noted that the LAP score was also low in patients with paroxysmal nocturnal hemoglobinuria (PNH), although this was not used as a diagnostic test for PNH. In the laboratory, the LAP score is determined using a cytochemical stain on a peripheral blood film followed by a semiquantitative visual estimation of the degree of staining in neutrophils. Thus, the test is inherently limited in its reproducibility and accuracy. Finally, even before the molecular pathogenesis of CML and PNH was fully understood, it was recognized that the LAP score may not always be low in CML and PNH, and can be low in some cases of other myeloproliferative neoplasms and myelodysplastic syndromes.

The current WHO classification of chronic myeloproliferative neoplasms does not use the LAP score at all (WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. IARC: Lyon 2008). CML is defined by the presence of the BCR/ABL-1 rearrangement, which underlies the pathogenesis of CML and is the basis of treatment of CML using tyrosine kinase inhibitors such as imatinib mesylate. If a myeloproliferative neoplasm is positive for the BCR/ABL-1 rearrangement, it is classified as CML, regardless of the LAP score. Just as a low LAP score does not make a diagnosis of CML, a normal or high LAP score doesn’t exclude it.

Current understanding of the pathogenesis of CML and PNH allows utilization of much more sensitive and specific tests for diagnosis. For suspected CML, BCR/ABL, Translocation 9;22, Fluorescence In Situ Hybridization (FISH) should be ordered. For suspected PNH, PI-Linked Antigen is the best laboratory test.

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