Chromosome 5q deletion syndrome is an acquired, hematological disorder characterized by loss of part of the long arm (

q arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total ...

, 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 181 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. C ...

in bone marrow myelocyte 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 immature 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 ...

. 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 reprodu ...

5q", though both conditions have been observed in the same family. This should not be confused with the

germ line In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...

cri du chat Cri du chat syndrome is a rare genetic disorder due to a partial chromosome deletion on chromosome 5. Its name is a French term ("cat-cry" or " call of the cat") referring to the characteristic cat-like cry of affected children. It was first de ...

(5p deletion) syndrome which is a deletion of the short arm of the 5th chromosome.

Presentation

The 5q-syndrome is characterized by

macrocytic anemia The term ''macrocytic'' is from Greek words meaning "large cell". A macrocytic class of anemia is an ''anemia'' (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their ...

, often a moderate

thrombocytosis Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. ...

, erythroblastopenia,

megakaryocyte A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In ...

hyperplasia 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 (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

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

pathogenesis 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 from Greek πάθος ''pat ...

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 or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

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 protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

-dependent and p53-independent

tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a 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 in a loss or re ...

effects. Other genes at this region include miR-145 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 microscopi ...

and

seen in 5q- syndrome;

SPARC SPARC (Scalable Processor Architecture) is a reduced instruction set computer (RISC) instruction set architecture originally developed by Sun Microsystems. Its design was strongly influenced by the experimental Berkeley RISC system develope ...

, which has antiproliferative and antiangiogenic effects; and the candidate tumor suppressors

EGR1 EGR-1 (Early growth response protein 1) also known as ZNF268 (zinc finger protein 268) 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 wa ...

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 m ...

, and CDC25C.

Histology

This syndrome affects bone marrow 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 bone marrow shows characteristic changes in the

megakaryocytes A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In hum ...

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

Diagnosis

Bone marrow biopsy

Treatment

Lenalidomide 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.

Prognosis

Most affected people have a stable clinical course but are often transfusion dependent.

References

External links

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