AML: Pathology | Medical Science Optional Notes for UPSC PDF Download

Myeloid Neoplasms

Neoplasms originating from hematopoietic progenitors, known as myeloid neoplasms, typically result in clonal proliferations that replace the normal cells in the bone marrow.

AML-FAB Classification

AUER Rods

• Auer rods are unique rod-like structures that stain red and may be found in myeloblasts or cells at more advanced stages of differentiation.
• They are notably abundant in cases of acute promyelocytic leukemia.

Auer rods are indicative of neoplastic myeloblasts, serving as a valuable diagnostic indicator when detected.

AML-WHO Classification

Acute myeloid leukemias (AMLs) exhibit diversity in terms of genetics, cellular lineage, and maturation levels. The World Health Organization (WHO) classification utilizes these features to categorize AML into four groups:

1. AMLs linked to specific genetic abnormalities, crucial for predicting outcomes and guiding therapy.
2. AMLs displaying dysplasia, many of which originate from myelodysplastic syndromes.
3. AMLs emerging post-genotoxic chemotherapy.
4. AMLs without the aforementioned features.

AMLs falling into the last category are further classified based on the predominant line of differentiation observed in the tumor.

AML-Etiology

Environmental Influences

• Benzene
• Ionizing radiation
• Tobacco, chemotherapy drugs

Genetic or Chromosomal Contributors

• Down syndrome
• t(15;17) translocation (notably associated with acute promyelocytic leukemia (M3))
• Fanconi anemia
• Philadelphia translocation (observed in less than 2% of AML patients)

AML-M31 (15;17)

The translocation t(15;17) leads to the fusion of the retinoic acid receptor alpha (RARA) gene on chromosome 17 with the PML gene on chromosome 15. This fusion results in the formation of a PML/RARalpha chimeric gene, generating a fusion protein that hinders myeloid differentiation at the promyelocytic stage, potentially by inhibiting the normal function of retinoic acid receptors.

Interestingly, therapeutic doses of all-trans retinoic acid (ATRA), an analog of vitamin A, can overcome this differentiation block, prompting the neoplastic promyelocytes to swiftly differentiate into neutrophils. As neutrophils have an average lifespan of about 6 hours, ATRA treatment rapidly eliminates the tumor.

Recent observations indicate that combining ATRA with arsenic trioxide, a substance that induces the degradation of the PML/RARA fusion protein, is more effective than ATRA alone. This combination achieves cures in over 80% of patients.

AML-Prognostic Factors

AML - Repeats

Give the FAB classification of acute myeloid leukemia and discuss the laboratory findings in a case of M3 AML. (2012)