An AML patient types heterozygous for HLA-A,B by serology but homozygous by molecular SBT. What explanation best accounts for this?

The scenario describes a situation in which a patient with acute myeloid leukemia (AML) presents differing results for HLA typing depending on the method used: serology indicating heterozygosity for HLA-A and HLA-B, while molecular sequence-based typing (SBT) suggests homozygosity. The most plausible explanation for this discrepancy lies in the nature of the patient's AML cells versus their normal lymphocytes.

In the context of acute myeloid leukemia, it is known that malignant cells can exhibit altered expression of HLA molecules. This can occur due to various changes in the tumor microenvironment or as a consequence of genetic mutations that affect HLA expression. Hence, the leukemic cells may express different HLA molecules or show a loss of HLA heterozygosity compared to the patient's own lymphocytes, which can lead to the variations found when using different typing methods.

The serological typing method relies on the presence of HLA antigens on the surface of cells, which may still reflect the heterozygous status of the patient's lymphocytes. Meanwhile, molecular SBT can provide a more accurate genetic representation of HLA typing, uncovering the homozygous status of the malignant cell population. This indicates that the AML cells