Medical Archive

Introduction

Myeloproliferative neoplasm MPN

Neoplastic proliferation of mature cells of myeloid lineage
Polycythemia vera(PV)
Primary Myelofibrosis(PMF)
Essential thrombocytosis(ET)
CML

• JAK2 mutation
  • PV 95%, PMF & ET 50%
  • Replaces VAL with PHE at the 617 position, rendering hematopoietic cells more sensitive to growth factors such as EPO and TPO.

Complication
Increased risk for hyperuricemia and gout due to high turnover of cells
Progression to marrow fibrosis or transformation to acute leukemia

Chronic myeloid leukemia CML
C101 Chronic Myeloid Leukemia
Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors; 
Basophils are characteristically increased

Polycythemia vera

Etiology

Normally, tissue hypoxia ? ?EPO ? activates JAK2 TK ? differentiates late myeloid cells into erythrocytes.

Primary : 97%?? JAK2 mutation ? constitutively active JAK2 gene ? EPO ??? RBC ??
Secondary
? ??(??) ???? ??? EPO ??
Renal artery stenosis, ?? ??? ?????? EPO ??
Relative : ?? ??? ????? RBC??? ? ?? ??

Clinical features

Hyperviscosity? ?? ??
Blurry vision and headache
Increased risk of venous thrombosis (e.g., hepatic vein, portal vein, and dural sinus)
Flushed face due to congestion (plethora)
Itching, especially after bathing (due to histamine release from increased mast cells)
Splenomegaly, Leukocytosis, Thrombcytosis? 1°???. (???? ? ??x)
Aquagenic pruritus (?? ??? ???), Erythromelalgia (??????)

Diagnosis

??: Hb 18.5-?, Hb 16.5-?
Hb 20, Hct 60?? relative erythrocytosis? ?? ??

Decreased EPO
Increased RBC mass & plasma volume
Normal SaO2

??????

RBC mass ??	EPO ??	SaO2 ??	??X or O + HbCO nl.	O2 affinity ??
??: relative –	??: ?????	??: ????!	Smoker’s polycythemia	??: tumor?

In reactive polycythemia due to ectopic EPO production from renal cell carcinoma, EPO is high, and SaO2 is normal.

Check RBC mass by 51Cr-tagged RBC infusion.

Complications

Treatment

• ????? phlebotomy (TOC), ??!!! ???: Hb 14-?, 12-?
• ???: ??????. ?? ??? INF
• Erythrocytosis, Thrombocytosis ??: hydroxyurea (IV line ?????)
• Ruxolitinib “???” – JAK1/2 inhibitor

Primary myelofibrosis

Chronic idiopathic myelofibrosis PMF
Neoplastic proliferation of mature myeloid cells, especially megakaryocytes
Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis

Etiology

Clinical features

• Weakness, fatigue, weight loss
• Splenomegaly: left upper quadrant abdominal pain 
• Hyperproliferative phase (early phase): thrombocytosis (? thromboembolic events) and leukocytosis
• Pancytopenic phase (late phase):

?????(??, ?, ???)? ?? ????? ??

• CBC: anemia, leukoerythroblastosis 
• Lab studies: ? leukocyte alkaline phosphatase, LDH, and uric acid
• PBS: dacrocytes (teardrop cells)
• BM aspiration: punctio sicca (“dry tap” – fail to aspirate)

Diagnosis

Megakaryocyte proliferation & atypia + ?? MPN ?? + JAK2 (+, 50%)

Complications

????? ????, 10%? Acute leukemia?
Bad Px: 70? ??, anemia, thrombocytopenia, ?? ??? ??, ????

Treatment

• Curative: allogeneic stem cell transplantation (option for younger patients)
• Supportive 
  • Hyperproliferative phase 
    • Prevent thromboembolisms: antiplatelet drug (aspirin 100 mg)
    • Control cell count: hydroxyurea, interferon alpha, cladribine
  • Pancytopenic phase 
    • JAK2 inhibitor: ruxolitinib 
    • Periodic transfusions 
    • Low-dose thalidomide plus glucocorticoids 

Essential thrombocytosis

Etiology

Clinical features

Cerebrovascular, ????? ??. Stroke? ? ??? ?? ?

Diagnosis

Plt >450,000
BM (+)
?? MPN ??|
JAK2 mutation (57%)

CML ? ?? MPD? ????? LAP ?

Rarely progresses to marrow fibrosis or acute leukemia
No significant risk for hyperuricemia or gout

Complications

Treatment

????(60? ??, ??? history, JAK+): cytoreductive therapy
Hydroxyurea + aspirin