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0 min readIntroduction
Acute Myeloid Leukemia (AML) is a heterogeneous group of malignant neoplasms of the blood and bone marrow characterized by the rapid proliferation of abnormal myeloid precursors. A specific subtype, Acute Promyelocytic Leukemia (APL), constitutes approximately 10-15% of all AML cases and is uniquely defined by the presence of the PML/RARA fusion gene resulting from a reciprocal translocation t(15;17)(q24.1;q21.2). This fusion gene disrupts normal myeloid differentiation, leading to an accumulation of promyelocytes. Accurate laboratory diagnosis is critical for prompt initiation of targeted therapy, significantly improving patient outcomes.
Laboratory Findings in Acute Myeloid Leukemia (PML/RARA) Fusion Gene Type (APL)
1. Peripheral Blood Examination
The peripheral blood findings in APL are often dramatic and characteristic:
- White Blood Cell (WBC) Count: Typically elevated, ranging from 10,000 to >100,000/µL. However, some cases can present with normal or even decreased WBC counts.
- Differential Count: Predominantly composed of promyelocytes (typically >90% of non-erythroid cells). Auer rods, needle-like crystalline inclusions within the cytoplasm of promyelocytes, are a hallmark finding.
- Platelet Count: Frequently decreased (<20,000/µL) due to consumption and bone marrow suppression. Thrombocytopenia is a major contributor to bleeding complications.
- Hemoglobin: Variable, ranging from normal to decreased, reflecting the degree of bone marrow involvement.
- Peripheral Smear: Presence of numerous promyelocytes with characteristic Auer rods. May also observe blasts and occasional myelocytes.
2. Bone Marrow Examination
Bone marrow aspiration and biopsy are essential for confirming the diagnosis:
- Cellularity: Typically hypercellular, with a marked proliferation of promyelocytes.
- M:E Ratio: Significantly increased myeloid to erythroid (M:E) ratio, often >10:1.
- Morphology: Predominance of atypical promyelocytes with abundant cytoplasm, finely granular chromatin, and prominent nucleoli. Auer rods are commonly observed.
- Immunophenotyping: APL cells typically express myeloid markers such as CD34, CD117, and HLA-DR, but lack expression of lineage-specific markers. CD38 is often strongly positive.
3. Cytochemical Staining
Cytochemical stains can aid in the diagnosis, although less frequently used with the advent of molecular techniques:
- Sudan Black B: Positive staining for Auer rods within the cytoplasm of promyelocytes.
- Myeloperoxidase (MPO): Positive staining in the cytoplasm of blasts and promyelocytes, confirming myeloid lineage.
- Periodic Acid-Schiff (PAS): Typically negative or weakly positive.
4. Molecular Genetic Studies
Molecular confirmation is crucial for definitive diagnosis and risk stratification:
- Reverse Transcription Polymerase Chain Reaction (RT-PCR): Detects the PML/RARA fusion transcript. This is the gold standard for diagnosis.
- Fluorescence In Situ Hybridization (FISH): Demonstrates the t(15;17) translocation directly by visualizing the fusion of the PML and RARA genes.
- Quantitative RT-PCR (qRT-PCR): Used for monitoring minimal residual disease (MRD) during and after treatment. Higher levels of PML/RARA transcript at diagnosis and during follow-up are associated with a higher risk of relapse.
5. Coagulation Studies
APL is frequently associated with Disseminated Intravascular Coagulation (DIC):
- Prothrombin Time (PT): Prolonged
- Activated Partial Thromboplastin Time (aPTT): Prolonged
- Fibrinogen: Decreased
- D-dimer: Elevated
| Test | Typical Finding in APL |
|---|---|
| WBC Count | Elevated (10,000 - >100,000/µL) |
| Promyelocytes (%) | >90% |
| Platelet Count | Decreased (<20,000/µL) |
| Auer Rods | Present |
| PML/RARA Transcript (RT-PCR) | Positive |
| PT/aPTT | Prolonged |
Conclusion
The laboratory findings in APL are distinctive and, when combined with clinical presentation, strongly suggest the diagnosis. Confirmation via molecular genetic studies (RT-PCR and/or FISH) is essential. Prompt diagnosis and initiation of targeted therapy, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), are crucial for achieving high remission rates and improving long-term survival. Monitoring for complications like DIC and MRD is also vital for optimal patient management.
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