Multifaceted Approach to the Diagnosis and Classification of Acute Leukemias

Abstract

Until recently, the diagnosis and classification of acute myeloid (AML) and acute lymphoblastic (ALL) leukemias was based almost exclusively on well-defined morphologic criteria and cytochemical stains. Although most cases can be diagnosed by these methods, there is only modest correlation between morphologic categories and treatment responsiveness and prognosis. The expansion of therapeutic options and improvement in remission induction and disease-free survival for both AML and ALL have stimulated emphasis on defining good and poor treatment response groups. This is most effectively accomplished by a multifaceted approach to diagnosis and classification using immunophenotyping, cytogenetics, and molecular analysis in addition to the traditional methods. Immunophenotyping is important in characterizing morphologically poorly differentiated acute leukemias and in defining prognostic categories of ALL. Cytogenetic and molecular studies provide important prognostic information and are becoming vitally important in determining the appropriate treatment protocol. With optimal application of these techniques in the diagnosis of acute leukemias, treatment strategies can be more specifically directed and new therapeutic approaches can be evaluated more effectively.

A systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (ALL)

“…These three methods are useful for first diagnosing a haemopoietic malignancy, then for determining the subtype of leukaemia, and finally for establishing the specific type of ALL. This final step is perhaps the most important because it aids in establishing the patient's risk profile, which, along with the clinical findings, will help determine treatment and prognosis (McKenna 2000). The French-American-British (FAB) classification system separates ALL cases into three groups based on the morphological characteristics of the tumour cells (Pui 1997;Pui & Evans 1998).…”

“…The French-American-British (FAB) classification system separates ALL cases into three groups based on the morphological characteristics of the tumour cells (Pui 1997;Pui & Evans 1998). Another system, the WHO classification scheme, has recently been revised, but its utility is debatable (McKenna 2000). The FAB system is outlined in Table 2.…”

“…The FAB system is outlined in Table 2. A small portion of cases cannot be properly diagnosed or classified without immunophenotyping (McKenna 2000). Newer techniques such as immunophenotyping allow for an examination of various tumour protein markers to better define the specific cellular subtype of ALL.…”

“…Conversely, patients (especially infants) with MLL rearrangements (for mixed lineage leukaemia or myeloid-lymphoid leukaemia), hypodiploidy, or the BCR-ABL gene fusion are at high risk. The BCR-ABL gene fusion is a consequence of a translocation between chromosomes 9 and 22, called the Sources: (Pui & Crist 1994;McKenna 2000).…”

The Vascular Endothelial Growth Factor (VEGF) Signaling Pathway: A Therapeutic Target in Patients with Hematologic Malignancies

“…Leukemias, myelodysplastic syndromes (MDS), lymphomas, and multiple myeloma (MM) are complex diseases with a wide range of clinical, morphologic, biologic, cytogenetic, molecular, and immunophenotypic features [1][2][3][4][5]. With this multitude of disease-associated variables, it is not surprising that response to treatment differs considerably among patients [6].…”