Hematologic Malignancies

Molecular testing in haematological malignancy supports diagnosis, risk stratification and the identification of targetable alterations, and is reported alongside morphological, immunophenotypic and cytogenetic findings.

Where molecular testing fits

Haematological malignancy is diagnosed and classified from several streams of evidence at once: morphology, immunophenotype, cytogenetics and molecular genetics. Molecular findings are reported alongside the others rather than in isolation, because current classifications define many entities by a combination of features rather than by a single marker.

Testing serves three distinct clinical purposes, and the purpose determines the assay. The first is diagnostic classification. The second is risk stratification, where the genotype refines a prognostic estimate that morphology alone cannot give. The third is identifying alterations for which a targeted agent or a clinical trial exists.

Myeloid neoplasms

Myeloid next-generation sequencing panels cover the genes recurrently altered in acute myeloid leukaemia, myelodysplastic neoplasms and myeloproliferative neoplasms. In suspected myeloproliferative neoplasm, JAK2, CALR and MPL testing addresses the driver question directly; these three are largely mutually exclusive and their assessment is a defined step in the diagnostic pathway.

Quantitative PCR for recurrent fusion transcripts supports both the initial identification of a fusion-defined entity and subsequent monitoring of the same target over time, where the transcript level is the quantity of clinical interest.

Lymphoid neoplasms

A dedicated chronic lymphocytic leukaemia panel addresses the alterations that carry prognostic and treatment-selection weight in CLL. IGHV somatic hypermutation status is assessed separately: it is a stable, once-in-a-disease-course determination that separates mutated from unmutated disease, and it continues to inform prognosis and treatment discussion.

T-cell and B-cell receptor repertoire and clonality assessment addresses a different question again — whether a lymphoid population is clonal. This is most useful where morphology and immunophenotype leave genuine ambiguity between a reactive and a neoplastic process.

Leukaemia and lymphoma NGS, including gene fusion detection, extends coverage to structural events that a sequence-only approach would miss.

Relationship to cytogenetics and to research

Molecular results are interpreted together with karyotype and FISH findings from Cytogenetics & Cytogenomics, since some defining lesions are visible cytogenetically and others only molecularly. Departmental research on the genomics of haematological malignancy sits within the Cancer Genetics & Genomics programme, and related publications are listed in the publication database.