Myeloid Neoplasms

Three broad categories of myeloid neoplasia:

• Acute myeloid leukemias in which an accumulation immature myeloid forms (blasts) in the bone marrow suppresses normal hematopoiesis.
• Myelodysplastic syndromes in which defective maturation of myeloid progenitors gives rise to ineffective hematopoiesis, leading to cytopenias
• Myeloproliferative disorder in which there is usually increased production of one or more types of blood cells

Acute Myeloid Leukemia (AML)
AML is a tumor of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to accumulation of immature myeloid blasts in the marrow. The replacement of the marrow with blasts produces marrow failure and complications related to anemia, thrombocytopenia and neutropenia.

AML classifications

1. AML with genetic aberration
2. AML with myelodysplatic syndrome-like feature
3. AML therapy related
4. AML otherwise not specified

Pathogenesis
Many of the recurrent genetic aberrations seen in AML disrupt genes encoding transcription factors that are required for normal myeloid differentiation. There is increasing evidence that mutations that lead to activation of growth factor signaling pathways collaborate with transcriptions factor aberrations to produce AML.
Immunophenotype
Because it can be difficult to distinguish myeloblasts and lymphoblasts morphologically, the diagnosis of AML confirmed by performing stains for myeloid-specific antigens.
Cytogenetics
Cytogenetic analysis has a central role in classification of AML.
Clinical features
Most patients present within weeks or few months of the onset of symptoms with complains related to anemia, neutropenia and thrombocytopenia, most notably fatigue, fever and spontaneous mucosal and cutaneous bleeding.
Prognosis
About 60% achieve complete remission with chemotherapy but only 15-30% remain free of disease for 5yrs.

Chronic myelogenous leukemia
Chronic myelogenous leukemia (CML) is distinguisched from other myeloproliferative disorders by the presence of a chimeric BCR-ABL gene (Philadelphia gene) derived from portions of the BRC gene on chromosome 22 and the ABL gene on chromosome 9.
Pathogenesis
BCR-ABL protein activates a cascade of proteins that control the cell cycle, speeding up cell division. Moreover the BCR-ABL protein inhibit DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities.
Clinical features
The onset is insidious. Mild to moderate anemia and hypermetabolism due to increased cell turnover lead to fatigability, weakness, weight loss and anorexia. Sometimes the first symptom is a dragging sensation in the abdomen caused by splenomegaly or the acute onset of left upper quadrant pain due to splenic infarction