Bit · Heme/Onc
Myeloproliferative Neoplasms — PV, ET, PMF, CML
Four clonal expansions of mature myeloid cells. Same family, four different cell lines run wild. The pivot is which cell line is overproduced and the molecular marker.
Mechanism
Myeloproliferative neoplasms (MPNs) are clonal expansions of mature hematopoietic cells. All originate from a hematopoietic stem cell mutation — three of them share JAK2 V617F mutations to varying degrees, while CML has its own translocation:
- Polycythemia vera (PV) — RBC overproduction (+ leukocytes + platelets). JAK2 V617F in >95%. Hyperviscosity, plethora, pruritus after hot shower (aquagenic), erythromelalgia, thrombosis. Treatment: phlebotomy + low-dose aspirin; hydroxyurea if high-risk.
- Essential thrombocythemia (ET) — platelet overproduction. JAK2, CALR, or MPL mutations. Often asymptomatic; thrombosis or bleeding (paradoxical, very high platelets cause acquired vWF deficiency). Treatment: aspirin; hydroxyurea if high-risk.
- Primary myelofibrosis (PMF) — marrow fibrosis driven by abnormal megakaryocyte cytokine release. Cytopenias, extramedullary hematopoiesis (massive splenomegaly), teardrop cells + leukoerythroblastic smear (immature granulocytes + nucleated RBCs). Dry tap on aspiration. Worst prognosis of the MPNs.
- CML — see that Bit. Philadelphia chromosome t(9;22), BCR-ABL, imatinib.
Differentiator Table
| Disease | Predominant cell | Driver mutation | Hallmark | Treatment |
|---|---|---|---|---|
| PV | RBCs | JAK2 V617F (>95%) | Aquagenic pruritus, plethora, ↑ Hct, thrombosis | Phlebotomy + low-dose aspirin; hydroxyurea if high-risk |
| ET | Platelets | JAK2 / CALR / MPL | Very high platelets, thrombosis OR bleeding | Aspirin; hydroxyurea |
| PMF | Marrow fibrosis | JAK2 / CALR / MPL | Teardrop cells, leukoerythroblastic smear, massive splenomegaly, dry tap | Ruxolitinib; HSCT in young |
| CML | Myeloid | BCR-ABL t(9;22) | Massive WBC at all maturation stages | Imatinib |
The Pivot
Two questions:
- Which cell line is up? RBC → PV. Platelets → ET. WBC with all stages → CML.
- Marrow fibrosis with teardrop cells and leukoerythroblastic smear? → PMF.
Molecular marker confirms: BCR-ABL = CML. JAK2 V617F = consistent with PV (or ET/PMF).
NBME-Style Stem
A 62-year-old man presents with itching after hot showers and reddish discoloration of his face. Hemoglobin is 19 g/dL, hematocrit 58%. JAK2 V617F mutation is positive. Erythropoietin level is suppressed. Which of the following is the most likely diagnosis?
Concept Anchor
Each MPN is one mature blood line cloned out of control. The cell that's high in the CBC plus the right driver mutation closes the diagnosis.