5q DeletionEdit

5q Deletion refers to a recurrent chromosomal abnormality in which a portion of the long arm (the q arm) of chromosome 5 is missing. It is most frequently encountered in hematologic disorders, notably within the spectrum of myelodysplastic syndromes (MDS), but it also occurs in some cases of acute myeloid leukemia (AML) and other myeloid neoplasms. A well-recognized subset of MDS with this abnormality is the so-called 5q- syndrome, which has distinct clinical and biological features and generally carries a more favorable prognosis than many other MDS subtypes. The condition illustrates how specific chromosomal losses disrupt normal hematopoiesis and shape treatment responses.

Mechanisms and Genetics - The 5q deletion varies in size and can involve several regions on the long arm of chromosome 5. The consequences reflect haploinsufficiency of multiple genes rather than loss of a single sole driver. In the best-characterized cases, the loss of one copy of particular genes disturbs erythroid and megakaryocytic development. - Key genes implicated in the pathogenesis include RPS14, located on 5q, which has been linked to the characteristic macrocytic anemia seen in many patients with the 5q- syndrome. Other genes on 5q, such as EGR1 and CSNK1A1, are also thought to contribute to disease biology and to specific morphologic features of the bone marrow. - The clinical manifestations arise from a combination of gene dosage effects and the other somatic alterations that commonly accompany the deletion. In many patients, the del(5q) clone exists with relatively few additional cytogenetic abnormalities, which helps explain why the 5q- syndrome can have a more favorable prognosis in some cases.

Clinical Features - 5q- syndrome is a distinctive presentation of MDS characterized by macrocytic anemia and often a relative preservation of platelet function with a tendency toward larger, dysplastic megakaryocytes. Patients frequently present with fatigue and pallor due to anemia. - Platelet counts in 5q- syndrome can be normal to elevated, and megakaryocytes in the bone marrow often show characteristic morphological abnormalities. - The disease tends to occur in older adults, and the natural history is typically more indolent than for many other MDS subtypes, particularly when the deletion is isolated (i.e., without complex additional chromosomal changes). - Response to targeted therapies, most notably lenalidomide, is a hallmark of the 5q- syndrome, and many patients achieve transfusion independence with treatment.

Diagnosis - Diagnosis relies on cytogenetic analysis of hematopoietic cells. Conventional karyotyping can detect the del(5q) abnormality, and targeted methods such as fluorescence in situ hybridization (FISH) for 5q can confirm the deletion even when cells are morphologically normal. - Molecular testing may identify cooperating mutations or assess gene dosage effects, while broader sequencing panels can help distinguish isolated del(5q) from more complex karyotypes. - Because the clinical presentation overlaps with other MDS subtypes, cytogenetic testing is a standard part of the initial workup for suspected MDS and for guiding prognosis and therapy.

Management and Treatment - For many patients with the 5q- syndrome, lenalidomide is the centerpiece of disease-modifying therapy. It can induce substantial anemia relief and transfusion independence in a large proportion of patients with isolated del(5q). Side effects and marrow suppression are considerations that require monitoring. - Supportive care remains integral: red blood cell transfusions, iron chelation in chronically transfused patients, and erythropoiesis-stimulating agents when appropriate are used to manage anemia. - In higher-risk or symptomatic cases, allogeneic hematopoietic stem cell transplantation (bone marrow transplantation) may be considered, particularly in younger patients or those with high-risk disease features. - Other treatments, such as hypomethylating agents or supportive care tailored to cytopenias, may be used in selected cases, depending on the overall risk assessment and patient goals.

Prognosis - The prognosis for del(5q) MDS varies with the broader cytogenetic context and the patient’s clinical features. In many cases of isolated del(5q), prognosis is comparatively favorable, with longer median survival than for many other MDS subtypes. - The achievement of transfusion independence with lenalidomide therapy and the absence of additional high-risk cytogenetic abnormalities are important positive prognostic factors. - The development of progression to AML or the acquisition of complex karyotypes can worsen prognosis, underscoring the importance of ongoing monitoring and risk stratification.

Epidemiology and History - Del(5q) is among the more frequently encountered recurrent cytogenetic abnormalities in MDS and is observed with varying frequency across patient cohorts. Its recognition as a distinct clinical and biological entity has guided both diagnostic classification and targeted therapeutic approaches. - The identification of the 5q- syndrome as a recognizable and clinically meaningful subset of MDS has helped tailor management strategies and underscored the value of cytogenetic profiling in hematologic diseases.

Controversies and debates - Classification and nomenclature have evolved as cytogenetic insights have grown. Some clinicians emphasize recognizing isolated del(5q) as a discrete clinical entity versus viewing it as part of a broader MDS spectrum with a favorable prognosis in selected contexts. - The use of lenalidomide, while standard for many del(5q) patients, is weighed against potential risks such as cytopenias, thromboembolism, or secondary malignancies in some settings. Debates continue about optimal sequencing of therapies, duration of treatment, and management of treatment-related adverse events. - The extent to which del(5q) should be considered in conjunction with molecular findings versus cytogenetic findings alone remains an area of active discussion, as integrated diagnostics become more common.

See also - myelodysplastic syndrome - 5q- syndrome - chromosome 5 - RPS14 - EGR1 - CSNK1A1 - lenalidomide - bone marrow transplantation - hematopoietic stem cell transplantation - karyotype - fluorescence in situ hybridization