Cytogenetic studies in acute leukemia – karyotypes
Frequent detection of changes in the karyotype in leukemic cells was a prerequisite for further progress in understanding the pathogenesis of acute leukemia, the development of diagnostic and prognostic models for various variants of acute leukemia, evaluating the effectiveness of therapy and detecting early recurrence.
The definition of karyotype has become the “gold standard” in diagnosing and predicting the course of acute leukemia.
In acute lymphoblastic leukemia, the presence of t (9; 22), determined in 30% of adult patients, t (4; ll), -7, or +8 (rarely observed) indicates an unfavorable prognosis. An altered karyotype is observed in approximately 80% of patients with acute myeloblastic leukemia. Detection in AML t (15; 17), t (8; 21) and inv (16) is prognostically favorable, while +8, -5, del (5q), -7, del (7q), -20, +11, +13, inv (3) and the involvement of llq23 are unfavorable signs.
Certain clinical variants of acute leukemia, such as M3, are associated with t (15; 17); myelocytic with maturation – with t (8; 21); acute myeloblastic leukemia with pathological bone marrow eosinophilia, with t (8; 14); t (2; 8); t (8; 22) with inv (16) or del 16p; megakaryocytic – with t (l; 22). Use for the treatment of podophyllotoxins or anthracyclines can lead to the appearance of translocations within 1–3 years after completion of chemotherapy. After alkylating drugs, the occurrence of -5, -7 and complex chromosomal abnormalities are most typical within 2-9 years after completion of therapy.
Genetic features (cytogenetic and molecular biological), along with other conditions (prior treatment, history of myelodysplastic syndrome (MDS)), significantly affect the course of acute leukemia, but are not always associated with the distinguished FAB categories. The drawbacks of the FAB classification led to the creation of a new classification that combines genetic and clinical aspects with morphology, cytochemistry and the immunophenotype of the hematopoietic system tumors. The work on its creation was completed in 1997 by a group of experts of the European Association of Hematopathology and the Society of Hematopathology.
The adopted WHO-classification is more rational: each selected nosological form has clinical significance and can be diagnosed by a pathologist.
Some specific cytogenetic disorders in acute myeloblastic leukemia (AML) are associated with typical morphology and affect the course of the disease. With the exception of the MoH with t (15; 17), they do not always correlate with the FAB category. This allowed us to identify four separate nosological units under the heading “acute myeloblastic leukemia (AML) with characteristic cytogenetic translocations.”
Cases with these cytogenetic disorders, but low blastosis, previously referred to as MDS, are classified as AML. It was decided to include in the WHO classification of AML with multilinear dysplasia, AML with a history of MDS, and AML associated with previous treatment.
In 2001, in accordance with the decision of the WHO commission, the preservation of FAB terminology and the separation of acute lymphoblastic leukemia (ALL) into forms L1, 2 and 3 was considered inexpedient, since the predictive value of morphological variants L1 and L2, as well as their correlation with the immunophenotype and cytogenetic markers are not obvious, and the form of L3 ALL is equivalent to Burkitt’s lymphoma in the leukemia phase.
Tumors from progenitor cells, regardless of whether they affect the lymph node or involve the bone marrow in the tumor process, are biologically the same. This led to the conclusion that ALL and lymphoblastic lymphoma are one disease with a different clinical picture. Due to the fact that in most cases, tumors from progenitor cells proceed with bone marrow damage, it was decided to abandon the term “acute lymphoblastic leukemia.”