Abnormal RH antigen expression in myeloid malignancies with MPL mutation, CSF3R mutation, or 1p deletion: Evidence of...

RH phenotype abnormalities, such as double populations or the loss of antigen expression, are frequently observed in the laboratory, especially as a result of blood transfusions or hematopoietic stem cell transplantation. Less commonly, these abnormalities may arise during the development of myeloid malignancies.

This study reports on 17 patients with RH phenotype abnormalities that could not be attributed to common causes. As part of the diagnosis or follow-up of their myeloid malignancies, molecular analyses, such as next generation sequencing (NGS) and single nucleotide polymorphism (SNP)-array, were performed.

Molecular analyses revealed abnormalities on chromosome 1p, including biallelic mutations in the MPL and CSF3R genes, as well as a deletion of the 1p region. These findings led to the identification of two molecular mechanisms responsible for the observed immunohematological abnormalities: the CN-LOH (Copy Neutral Loss of Heterozygosity) and the deletion of chromosome 1p.

CN-LOH of chromosome 1p, resulting in homozygosity for the MPL mutation, has been previously described in the literature. However, we report here for the first time a link between CN-LOH of chromosome 1p (resulting in homozygosity for the CSF3R mutation) or chromosome 1p deletion and the presence of RH phenotype abnormalities. Furthermore, no alloimmunization was observed despite increased transfusion requirements.