Clinical Hematology Series

Myeloid Neoplasms

Myeloproliferative neoplasms and myelodysplastic syndromes — classification and management.

15 slides·English·2026
Download PDF
Slides
0%
Title slide over a background of red blood cells, introducing a clinical guide to myeloid neoplasms.
01 / 15

Myeloproliferative Neoplasms (MPNs) & Myelodysplastic Syndromes (MDS)

A Clinical Guide to Classification, Pathophysiology, and Management

“For the learners… Classify.”

Based on Student Notes / HK 2022

Diagram breaking the term MYELO-PROLIFERATIVE NEOPLASM into three bracketed components, with a hematopoietic cell lineage illustration.
02 / 15

Deconstructing the Pathology

The term MYELO-PROLIFERATIVE NEOPLASM is deconstructed into three components:

  • Myeloid Lineage Origin — Non-Lymphoid: RBCs, Platelets, Neutrophils, Eosinophils, Basophils.
  • Increased Numbers — Manifests as -cytosis, -cythemia, or -philia.
  • Clonal Mutation — Autonomous growth. NOT Reactive. NOT Secondary.

Key Insight: Cancer is a clonal, genetic disease that arises from a normal counterp[art] [text cut off at slide edge].

Five-step signaling diagram showing a growth factor binding a receptor, JAK activation, STAT phosphorylation and dimerization, nuclear DNA binding, and controlled proliferation.
03 / 15

The Physiology of Proliferation

Normal Regulation: Supply Meets Demand

Hematopoietic progenitors only proliferate when the body requests it via cytokines.

Signaling cascade (growth factors EPO / TPO / GCSF):

  1. Ligand Binding — growth factor binds the receptor.
  2. Activation — Phosphorylation (JAK).
  3. Signal Transduction — STAT Dimerization.
  4. Gene Expression — STAT Binds to DNA (in the Nucleus).
  5. Result — Controlled Proliferation.
Side-by-side cell diagrams contrasting normal EPO-dependent JAK2 signaling with constitutively active mutant JAK2 in polycythemia vera.
04 / 15

The Pathophysiology: A Broken Switch

Normal Regulation

  • Erythropoietin binds its receptor; phosphorylated JAK2 dimers drive the JAK2 signaling pathway.
  • Leads to Activation of genes for growth/proliferation.
  • Negative feedback regulation is intact.
  • Dependent on Growth Factors.

Polycythemia Vera (MPN)

  • JAK2 mutant drives the JAK2 signaling pathway without ligand.
  • Leads to Dysregulated gene activation.
  • Negative feedback is lost (indicated by “?”).
  • Constitutive Activation (JAK2 V617F). Independent of Growth Factors.

The Result: Unregulated, clonal production of blood cells.

Flowchart classifying myeloproliferative neoplasms by Philadelphia chromosome status into CML and the classical Ph-negative MPNs.
05 / 15

The WHO Classification of Myeloid Neoplasms

Myeloproliferative Neoplasms (MPN) divide by Philadelphia chromosome status:

  • Philadelphia Chromosome (+)
    • CML (Chronic Myeloid Leukemia)
  • Philadelphia Chromosome (−) → Classical MPNs:
    • Polycythemia Vera (PV) — JAK2 V617F+ (95%) or Exon 12
    • Essential Thrombocythemia (ET) — JAK2 (50-70%), CALR, or MPL
    • Primary Myelofibrosis (PMF) — JAK2, CALR, or MPL
A balance scale weighing reactive/secondary causes against clonal/primary causes of high blood counts.
06 / 15

The Diagnostic Challenge: Reactive vs. Clonal

Is this high count secondary to stress, or is it cancer?

REACTIVE (Secondary)

  • Infection
  • Inflammation
  • Tissue Necrosis
  • Stress/Hypoxia
  • Smoking
  • Medications

Neutrophil counts >50k usually indicate non-reactive etiologies.

CLONAL (Primary)

  • Myeloproliferative Neoplasms (Mutations)

The Clinical Question: Differentiating the cause of Cytosis/Cythemia.

Diagnostic flowchart for high hemoglobin using erythropoietin level to separate secondary from primary polycythemia, ending in a JAK2-positive diagnosis.
07 / 15

Case Study 1: Erythrocytosis (Polycythemia)

Hb: 18.4 g/dL (High) | Hct: 54.4% (High)

Next step: Measure Erythropoietin (EPO).

  • High EPO → Secondary Polycythemia:
    • Lung disease
    • Altitude
    • Renal tumors
  • Low EPO → Primary Polycythemia (PV). Next Action: Test for JAK2 Mutation.

Patient Result: EPO 1.6 mIU/mL (Low) + JAK2 V617F Detected = Polycythemia Vera.

Case description of chronic myeloid leukemia beside a blood smear showing numerous mature granulocytes among red cells.
08 / 15

Case Study 2: Neutrophilia & Splenomegaly

Patient Profile: 31-year-old male. Incidental abnormal CBC.

Key Finding: Palpable Splenomegaly (50-90% of cases).

Diagnosis: Chronic Myeloid Leukemia (CML).

Clinical Features:

  • Insidious onset, fatigue, weight loss.
  • Hyperleukocytosis is tolerated due to mature, small cells.

Phases: Chronic -> Accelerated -> Blast Phase.

Case of essential thrombocythemia with a DNA double-helix illustration labeled Calreticulin (CALR) Mutation.
09 / 15

Case Study 3: Thrombocytosis

When JAK2 is negative, look for CALR.

Patient Profile: 30-year-old female, history of early pregnancy loss. Persistent high platelet count.

Differential Diagnosis:

  • Reactive: Iron deficiency, Infection, Inflammation.
  • Primary: Essential Thrombocythemia (ET).

Calreticulin (CALR) Mutation.

Diagnostic Breakthrough: Patient tested CALR Positive. Confirms Clonality in Ph-Negative MPNs.

Body silhouette with labeled callouts linking MPN complications to CNS, hepatic vein, limbs, and cardiovascular sites.
10 / 15

Clinical Features & Complications

The burden of disease beyond the blood counts.

  • CNS Symptoms (Headache, Dizziness, Visual disturbances)
  • Budd-Chiari Syndrome (Hepatic vein thrombosis) – A Red Flag for MPN
  • Erythromelalgia (Burning pain), Gout
  • Thrombosis (Stroke, MI, DVT) - 20% Risk
  • Progression to Fibrosis or Acute Leukemia (Blast Phase)
Two contrasting equations showing MPN yielding effective proliferation with high counts versus MDS yielding ineffective proliferation with low counts.
11 / 15

The Counterpoint: Myelodysplastic Syndromes (MDS)

MPN: Effective Proliferation — Mutation + Clonal Cytosis + UP (High Counts) = EFFECTIVE Proliferation.

MDS: Ineffective Proliferation (Dysplasia) — Mutation + Clonal Cytopenia + DOWN (Low Counts) = INEFFECTIVE Proliferation (Dysplasia).

Key Features List for MDS:

  • Acquired somatic mutations in stem cells.
  • Dysplasia: Abnormal maturation/morphology.
  • Disease of aging.
  • Presentation: Pancytopenia or single lineage cytopenia.
MDS case with three blood-smear micrographs illustrating anisopoikilocytosis, hypogranulated neutrophils, and basophilic stippling.
12 / 15

Case Study: MDS & Refractory Anemia

  • Patient: 80-year-old woman.
  • Presentation: Macrocytic anemia (Hb 7.4 g/dL, MCV 119.9 fL).
  • History: Failed Vitamin B12 treatment (Rules out nutritional cause).
  • Bone Marrow: Hypercellular (trying to grow) but Ineffective.

Blood smear findings:

  • Anisopoikilocytosis (Size/shape variation)
  • Hypogranulated Neutrophils (Abnormal, ‘washed out’ appearance)
  • Basophilic Stippling
Four-quadrant grid outlining primary prevention, thrombosis management, cytoreduction, and targeted therapy for MPNs.
13 / 15

Management Strategy for MPNs

Primary Prevention

Aspirin (Vascular event reduction)

Thrombosis Management

Systemic Anticoagulation

Cytoreduction

Hydroxyurea, Interferon. Venesection (Phlebotomy) for Polycythemia Vera.

Targeted Therapy

JAK2 Inhibitors (Ruxolitinib) for MPN. TKIs (Imatinib) for CML.

Numbered five-point summary recapping context, definition, genetics, differentiation, and risk for myeloid neoplasms.
14 / 15

Summary & Recap

  1. Context: The majority of high blood counts are Reactive/Secondary, not cancer.
  2. Definition: MPNs are Clonal, autonomous, and growth-factor independent.
  3. Genetics: JAK2 V617F, CALR, and MPL are the diagnostic keys for Classical MPNs.
  4. Differentiation: MDS represents clonal but ineffective hematopoiesis (Dysplasia + Cytopenia).
  5. Risk: Management focuses on preventing Thrombosis and monitoring for Fibrosis/Leukemic transformation.
Closing slide with contact email over a faint blood-cell background.
15 / 15

Questions & References

Contact: halkhaldy@kku.edu.sa

Thank you.