Hematologic Malignancies and Molecular Hematopathology
Concepts
Know the molecular hallmarks of hematologic neoplasms: BCR-ABL1 (CML, Ph+ ALL), PML-RARA (APL), RUNX1-RUNX1T1, CBFB-MYH11, and the role of JAK2 V617F, CALR, and MPL in myeloproliferative neoplasms. Understand clonality assessment (Ig/TCR gene rearrangement, X-inactivation), minimal residual disease (MRD) monitoring by RQ-PCR or NGS, and the distinction between diagnostic, prognostic, and monitoring markers.
Interpretation
Be able to interpret quantitative transcript levels (international scale for BCR-ABL1), the meaning of major molecular response, and the pitfalls of a rising transcript (assay variability vs true relapse). Understand FLT3-ITD (prognostic, allelic ratio), NPM1, CEBPA, TP53, and IDH1/2 in AML, and the role of MYD88 L265P in lymphoplasmacytic lymphoma. Know the difference between a clonal marker and a disease-defining lesion.
Traps
Items confuse a diagnostic marker with a monitoring marker, over-interpret a single low-level positive result, or ignore the need for a baseline sample to establish the clonal target. Watch for questions about the International Scale, conversion factors, and the requirement for a minimum sensitivity (often 4-5 log).
Rule of thumb
For MRD, always establish the baseline clone and its assay sensitivity before monitoring; a result below the limit of quantification should be reported as detected-but-not-quantifiable, not as a relapse. For BCR-ABL1, use the International Scale and require confirmed rising values on repeat testing.
Worked example
A CML patient on TKI has BCR-ABL1 rising from 0.01% to 0.05% IS on one draw. Do not declare relapse; repeat to exclude technical variation, assess adherence, and consider mutation analysis if the rise is confirmed.