Chromosome 5q deletion syndrome is an acquired, hematological disorder characterized by loss of part of the long arm ( q arm, band 5q33.1) of human

chromosome 5 Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 182 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. Ch ...

in bone marrow

myelocyte A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (can be found in circulating blood when caused by certain diseases). Structure When stained with the usual dyes, the cytoplasm is distinctly basophili ...

cells. This chromosome abnormality is most commonly associated with the

myelodysplastic syndrome A myelodysplastic syndrome (MDS) is one of a group of cancers in which blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may includ ...

. It should not be confused with "partial

trisomy A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes). Description and causes Most organisms that reprod ...

5q", though both conditions have been observed in the same family. Diagnosis is achieved through marrow biopsy.

Presentation

The 5q-syndrome is characterized by

macrocytic anemia Macrocytic anemia is a condition and blood disorder characterized by the presence of predominantly larger-than-normal erythrocytes (red blood cells, or ''RBCs'') accompanied by low numbers of RBC, which often carry an insufficient amount of hemogl ...

, often a moderate

thrombocytosis In hematology, thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150 to 450 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 7 ...

, erythroblastopenia,

megakaryocyte A megakaryocyte () is a large bone marrow cell with a lobation, lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal blood coagulation, clotting. In humans, megakaryocytes usually account for 1 out of 10,00 ...

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of Tissue (biology), organic tissue that results from ...

with

nuclear Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space *Nuclear ...

hypolobation, and an isolated interstitial deletion of chromosome 5. The 5q- syndrome is found predominantly in females of advanced age.

Causes

Several

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s in the deleted region appear to play a role in the

pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...

of 5q-syndrome.

Haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

of RPS14 plays a central role, and contributes to the

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

via both

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

-dependent and p53-independent

tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...

effects. Other genes at this region include

miR-145 In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. Targets MicroRNAs are involved in down-r ...

and miR-146a, whose deletion is associated with the megakaryocytic

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...

and

seen in 5q- syndrome; SPARC, which has antiproliferative and antiangiogenic effects; and the candidate tumor suppressors

EGR1 EGR-1 (Early growth response protein 1) or NGFI-A (nerve growth factor-induced protein A) is a protein that in humans is encoded by the ''EGR1'' gene. EGR-1 is a mammalian transcription factor. It was also named Krox-24, TIS8, and ZENK. It was or ...

CTNNA1 αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the ''CTNNA1'' gene. αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions to ...

, and

CDC25C Cdc25 is a dual-specificity phosphatase first isolated from the yeast ''Schizosaccharomyces pombe'' as a cell cycle defective mutant. As with other cell cycle proteins or genes such as Cdc2 and Cdc4, the "cdc" in its name refers to "cell divis ...

Histology

This syndrome affects

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

cells causing treatment-resistant

and

s that may lead to

acute myelogenous leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...

. Examination of the

shows characteristic changes in the

megakaryocytes A megakaryocyte () is a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but ca ...

. They are more numerous than usual, small and mononuclear. There may be accompanying erythroid hypoplasia in the bone marrow.

Treatment

Lenalidomide Lenalidomide, sold under the brand name Revlimid among others, is a medication used to treat multiple myeloma, smoldering myeloma, and myelodysplastic syndromes (MDS). For multiple myeloma, it is a first-line treatment, and is given with dexa ...

has activity in 5q- syndrome and is

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk

(MDS) associated with chromosome 5q deletion with or without additional cytogenetic abnormalities. There are several possible mechanisms that link the

haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

molecular lesions with lenalidomide sensitivity.

References

External links

* {{Myeloid malignancy, us=y Myeloid neoplasia Rare genetic syndromes Autosomal monosomies and deletions Syndromes affecting blood