Leukemia is a collective term for cancers that begin in the blood-forming tissues, specifically the bone marrow. This disorder involves the rapid, uncontrolled production of abnormal white blood cells, which interfere with the production of healthy blood cells. Since leukemia is not a single disease, a precise diagnosis requires a sequence of tests. These tests are designed to confirm the presence of cancerous cells and determine the exact subtype. The diagnostic process moves systematically from initial physical clues and simple blood work to specialized laboratory analysis of the bone marrow.
Initial Evaluation and Screening Blood Tests
The diagnostic process begins with a physician conducting a physical examination and reviewing the patient’s medical history. The doctor looks for physical signs suggesting blood cell abnormalities, such as unexplained bruising or paleness resulting from low platelet and red blood cell counts. Swelling in the lymph nodes, spleen, or liver is also checked, as abnormal blood cells can accumulate in these areas.
The first laboratory screening test is typically a Complete Blood Count (CBC), which analyzes the patient’s blood components. The CBC measures the number of white blood cells, red blood cells, and platelets circulating in the bloodstream. Abnormal findings, such as a significantly high or very low white blood cell count, anemia, or thrombocytopenia, raise suspicion for a bone marrow disorder.
A peripheral blood smear is often performed alongside the CBC, where a technician views a drop of blood under a microscope. The presence of blast cells—immature white blood cells—is a strong indicator of acute leukemia. The CBC and blood smear are screening tools that prompt the need for a definitive diagnostic procedure.
The Bone Marrow Biopsy and Aspirate
To definitively diagnose leukemia, doctors must examine the bone marrow, where blood cells are produced. This is done through a bone marrow examination, which involves both an aspirate and a biopsy. The procedure is typically performed by inserting a special needle into the back of the hip bone (posterior iliac crest) after applying a local anesthetic.
The bone marrow aspirate uses a syringe to withdraw a small, liquid sample of the marrow containing blood-forming cells. Following the aspirate, the doctor performs the bone marrow biopsy, using a hollow needle to remove a small, solid core of bone tissue and marrow.
The liquid aspirate provides individual cells necessary for detailed genetic and molecular testing. The solid core biopsy allows pathologists to examine the overall structure and cellularity of the marrow tissue. Combining both samples is necessary because the aspirate can sometimes fail to yield enough cells (a “dry tap”). The results of this examination confirm the diagnosis by determining the percentage of abnormal blast cells present in the marrow.
Laboratory Analysis for Leukemia Typing
Once collected, bone marrow samples undergo specialized laboratory tests to precisely classify the leukemia subtype. This detailed typing is necessary because the specific treatment regimen depends entirely on the nature of the cancer cells.
Flow Cytometry
One specialized test is flow cytometry, which rapidly analyzes thousands of cells from the aspirate sample. This technique identifies specific proteins, called cluster of differentiation (CD) markers, on the surface of the leukemia cells. This process, known as immunophenotyping, determines the cell’s lineage (lymphoid or myeloid) and is crucial for distinguishing between major types like Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL).
Cytogenetics
Another specialized analysis is cytogenetics, which examines the chromosomes within the leukemia cells for structural abnormalities. This test can reveal translocations, where parts of two different chromosomes have switched places. An example is the Philadelphia chromosome, a translocation between chromosomes 9 and 22. The presence of specific chromosomal changes affects the prognosis and determines eligibility for certain targeted therapies.
Molecular Analysis
A third category of testing is molecular analysis, which looks for smaller genetic mutations and gene fusions that are not detectable by standard cytogenetics. This includes techniques like polymerase chain reaction (PCR) and next-generation sequencing (NGS). These methods identify specific gene mutations that drive the cancer’s growth. Identifying these molecular markers is important for tailoring treatment, as some mutations indicate a more aggressive disease while others suggest responsiveness to particular targeted drugs.
Final Diagnosis and Risk Assessment
The definitive diagnosis of leukemia is reached when the hematologist synthesizes all information from the initial evaluation and specialized laboratory tests. This synthesis includes the patient’s symptoms, CBC results, the microscopic appearance of cells in the bone marrow aspirate, and the detailed genetic profile from molecular and cytogenetic studies. The final diagnosis specifies the classification of the leukemia, often including a specific gene mutation.
This comprehensive data set is then used for risk stratification, which determines the likely behavior of the disease and guides the initial treatment plan. Specific genetic abnormalities may place a patient into a favorable, intermediate, or adverse risk group. This stratification influences the intensity and type of chemotherapy or other therapies chosen. The diagnostic process confirms the cancer and provides a roadmap for the subsequent personalized treatment strategy.