Acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia (AML). It develops when immature white blood cells called promyelocytes accumulate in the bone marrow, the soft tissue inside bones where blood cells are made. This buildup crowds out healthy cells, preventing the blood from functioning properly. APL is a medical emergency because it often causes a severe bleeding disorder. Despite its aggressive nature, advances in targeted therapies have made APL the most curable form of adult leukemia, making prompt diagnosis a priority.
Presenting Signs and Symptoms
The most telling signs of APL stem from coagulopathy, a disorder that disrupts the body’s ability to form blood clots. Individuals may notice they bruise easily or experience severe, prolonged bleeding from minor cuts. Frequent nosebleeds or bleeding from the gums are also common. These bleeding problems arise because leukemic cells release proteins that interfere with clotting, leading to a high risk of both excessive bleeding and blood clot formation (thrombosis).
Beyond bleeding, symptoms reflect the bone marrow’s failure to produce enough healthy blood cells. A shortage of red blood cells (anemia) can cause profound fatigue, weakness, and pale skin. A low count of functional white blood cells (neutropenia) compromises the immune system, leading to frequent infections and fevers. When platelet levels are low, tiny, pinpoint-sized red spots called petechiae may appear on the skin.
Initial Laboratory Tests
When APL is suspected, initial laboratory tests are performed. The first is a complete blood count (CBC) with a differential, which measures the quantities of red cells, white cells, and platelets. In APL, the CBC often reveals pancytopenia, a deficiency in all three cell types, though the white blood cell count can sometimes be elevated.
A peripheral blood smear is performed alongside the CBC, where a pathologist examines blood cells under a microscope. This inspection can reveal the abnormal promyelocytes characteristic of APL. These cells often contain many granules and may display distinctive crystal-like structures called Auer rods, a strong indicator of this leukemia.
A coagulation panel is an urgent part of the workup. These tests assess clotting ability and include measurements like Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and fibrinogen levels. In APL, these studies often show results consistent with disseminated intravascular coagulation (DIC), where the clotting system is over-activated, leading to both bleeding and clotting.
Definitive Diagnostic Procedures
While initial tests raise suspicion, a conclusive diagnosis requires specialized procedures. The primary method is a bone marrow aspiration and biopsy, where a physician withdraws liquid marrow (aspiration) and solid marrow tissue (biopsy) from the hip bone. Examining the marrow provides a direct view of the cancerous cells and their concentration.
The bone marrow samples undergo microscopic analysis, where pathologists look for the features of APL cells, like their size, shape, and abundant granules. The identification of numerous promyelocytes containing multiple Auer rods is a finding that points toward an APL diagnosis.
Cytogenetic analysis is performed to confirm the underlying genetic cause by examining the cancer cell chromosomes. APL is defined by a specific genetic abnormality: a translocation between chromosome 15 and chromosome 17, denoted as t(15;17). This means a piece of chromosome 15 has swapped places with a piece of chromosome 17. A faster technique called Fluorescence In Situ Hybridization (FISH) can detect this translocation within hours, which is important for starting treatment quickly.
The most definitive test is a molecular analysis using polymerase chain reaction (PCR). This test looks for the specific abnormal fusion gene created by the t(15;17) translocation, which joins the PML gene on chromosome 15 with the RARA gene on chromosome 17. The resulting PML-RARA fusion gene is responsible for halting the maturation of promyelocytes. Detecting this gene confirms the diagnosis and is later used to monitor treatment effectiveness.
Risk Stratification Post-Diagnosis
Once APL is confirmed, the disease is classified into a risk category to guide the treatment plan. This risk stratification is based on the white blood cell (WBC) count at diagnosis, as this number correlates with the likelihood of certain complications.
The most widely used model sorts patients into two main groups based on their WBC count. Patients with a count of 10,000 per microliter of blood (≤10,000/mcL) or less are classified as low risk. Those with a count greater than 10,000/mcL are considered high risk.
A higher WBC count signifies a greater burden of leukemia cells and is associated with a higher probability of complications during initial treatment. High-risk patients have an increased chance of differentiation syndrome, a reaction to therapy that can cause respiratory distress and fluid retention. They also face a greater risk of thrombosis (blood clots). The risk level helps physicians anticipate these challenges and adjust the treatment strategy.