STEPTRACKERHEMATOLOGY + ONCOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Myeloproliferative Neoplasms

Clonal stem cells overproduce mature myeloid cells — too many red cells, platelets or granulocytes, and later a scarred marrow.

FOCUS ON
Name each neoplasm by the line that's high and its mutation: CML = BCR-ABL. PV = JAK2 (~95%), high RBCs and low EPO. ET = very high platelets (JAK2, CALR, MPL). Myelofibrosis = teardrop cells, dry tap, massive spleen. All risk thrombosis, gout, and transformation to AML.
NEOPLASM
KEY MUTATION
FEATURES
LABS · TREATMENT
Shared features
all MPNs
Clonal hematopoietic stem cell; growth-factor independence.
Splenomegaly, thrombosis and bleeding, gout (high cell turnover)
Can progress to myelofibrosis or AML
CML
BCR-ABL t(9;22)
↑ granulocytes at every stage, basophilia, often thrombocytosis; splenomegaly
↓ LAP · imatinib
Polycythemia vera
JAK2 V617F (~95%)
↑ RBC mass (often ↑ WBC and platelets); aquagenic pruritus, facial plethora, erythromelalgia, hyperviscosity → thrombosis (Budd-Chiari, stroke, MI), gout
↓ EPO · phlebotomy, aspirin, hydroxyurea, ruxolitinib
Essential thrombocythemia
JAK2 (~50%), CALR, MPL
Platelets > 450,000 (often > 1 million); thrombosis and bleeding (huge platelet mass absorbs vWF); erythromelalgia
Exclude reactive causes first · aspirin, hydroxyurea, anagrelide
Primary myelofibrosis
JAK2, CALR, MPL
Megakaryocytes release PDGF and TGF-β → marrow fibrosis → extramedullary hematopoiesis → massive splenomegaly
Teardrop cells, leukoerythroblastic smear, dry tap · ruxolitinib, transplant
Spent-phase / transformation
Clonal evolution
PV and ET can progress to myelofibrosis; any MPN can become AML
Falling counts + new splenomegaly or blasts
Reactive look-alikes
No clonal mutation
Reactive thrombocytosis (iron deficiency, inflammation, after splenectomy); secondary polycythemia (hypoxia, EPO tumors)
Check ferritin, CRP, EPO, SaO₂

Mechanism — signaling stuck on

EPO / TPO / G-CSF receptors
→
JAK2 V617FAlways active
→
STAT signalingNo ligand needed
→
OverproductionRBCs, platelets, granulocytes
Megakaryocytes ↑PDGF, TGF-β
→
FibrosisDry tap
→
Spleen and liver take overMassive splenomegaly

The JAK2-type MPNs compared

FEATURE
PV
ET
MYELOFIBROSIS
Main finding
↑ RBC mass
↑ platelets
Fibrosis, later cytopenias
Mutation
JAK2 ~95%
JAK2, CALR, MPL
JAK2, CALR, MPL
Smear
Often ↑ all lines
Large platelets
Teardrops, leukoerythroblastic
Spleen
Mildly ↑
Mildly ↑
Massive
Main risk
Thrombosis
Thrombosis + bleeding
Marrow failure, AML

How it's tested

COMMON CONFUSIONA low EPO with a high hematocrit points to PV. Secondary polycythemia has a high EPO.
THE TRAPA young woman with hepatic vein thrombosis and a borderline-high hematocrit may have occult PV. Test for JAK2 — and for PNH.
YOUR APPROACHWhich line is high? → rule out reactive causes → mutation (BCR-ABL, then JAK2/CALR/MPL) → watch for fibrosis and AML.

If you see… think…

Itching after a hot shower, ruddy face, ↑ Hct, ↓ EPO → polycythemia vera
Burning, red fingers relieved by aspirin → erythromelalgia (PV/ET)
Platelets 1.2 million, normal ferritin and CRP → essential thrombocythemia
ET patient with mucosal bleeding → acquired vWD from huge platelet mass
Massive spleen, teardrop cells, dry tap → primary myelofibrosis
Young woman with Budd-Chiari → check JAK2
MPN patient with an acutely swollen big toe → gout (cell turnover)
Granulocytes at all stages + basophilia + BCR-ABL → CML
JAK1/2 inhibitor for myelofibrosis → ruxolitinib