Dominant T-cell Receptor Delta Rearrangements in B-cell Precursor Acute Lymphoblastic Leukemia: Leukemic Markers or Physiological γδ T Repertoire?
Acute lymphoblastic leukemia (ALL) is an aggressive hematological malignancy characterized by clonal expansion of aberrant B- and T-cell precursor lymphoid cells. Rearranged immunoglobulin or T-cell receptor (IG/TR) genes represent a DNA fingerprint of each lymphoid clone and are reliable markers for monitoring physiological and leukemic lymphocyte populations. Minimal or measurable residual disease (MRD) is the most important prognostic parameter predicting ALL relapse and is used for risk stratification and therapy adjustment. Therefore, accurate identification of leukemic IG/TR rearrangements for monitoring MRD is of high clinical importance. However, the reliable distinction of leukemia-associated IG/TR rearrangements from other clonally expanded lymphocyte populations is often complex and requires careful consideration, particularly due to the possibility of oligoclonality and the presence of cross-lineage IG/TR rearrangements in precursor leukemias. Both phenomena are presumably a consequence of aberrant, persisting recombination processes in malignant immature lymphoid cells. Depending on patients age and ALL subtype, a considerable number of B-cell precursor ALL (BCP-ALL) harbor TR cross-lineage rearrangements. For instance, TR delta (TRD) gene rearrangements occur in 40%–90% of BCP-ALL as cross-lineage rearrangements, especially
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