Chromosome 5q deletion syndrome

Other names: Chromosome 5q monosomy, 5q- syndrome
Photomicrograph of bone marrow showing abnormal mononuclear megakaryocytes typical of 5q- syndrome

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 in bone marrow myelocyte cells. This chromosome abnormality is most commonly associated with the myelodysplastic syndrome.

It should not be confused with "partial trisomy 5q", though both conditions have been observed in the same family.[1] This should not be confused with the germ line cri du chat (5p deletion) syndrome which is a deletion of the short arm of the 5th chromosome.[citation needed]

## Contents

* 1 Symptoms and signs
* 2 Causes
* 3 Histology
* 4 Diagnosis
* 5 Treatment
* 6 Prognosis
* 7 References
* 8 External links

## Symptoms and signs[edit | edit source]

The 5q-syndrome is characterized by macrocytic anemia, often a moderate thrombocytosis, erythroblastopenia, megakaryocyte hyperplasia with nuclear hypolobation, and an isolated interstitial deletion of chromosome 5. The 5q- syndrome is found predominantly in females of advanced age.[2]

## Causes[edit | edit source]

Several genes in the deleted region appear to play a role in the pathogenesis of 5q-syndrome.[3][4] Haploinsufficiency of RPS14 plays a central role, and contributes to the anemia via both p53-dependent and p53-independent tumor suppressor effects.[4] Other genes at this region include miR-145 and miR-146a, whose deletion is associated with the megakaryocytic dysplasia and thrombocytosis seen in 5q- syndrome;[5] SPARC, which has antiproliferative and antiangiogenic effects; and the candidate tumor suppressors EGR1, CTNNA1, and CDC25C.[4]

## Histology[edit | edit source]

This syndrome affects bone marrow cells causing treatment-resistant anemia and myelodysplastic syndromes that may lead to acute myelogenous leukemia. Examination of the bone marrow shows characteristic changes in the megakaryocytes. They are more numerous than usual, small and mononuclear. There may be accompanying erythroid hypoplasia in the bone marrow.[6]

## Diagnosis[edit | edit source]

The diagnosis of this condition is based on the following:[7]

* Medical history
* Medical exam
* Lab test
* Genetic test

## Treatment[edit | edit source]

Mechanisms and potential new therapeutic targets

Lenalidomide has activity in 5q- syndrome[8] and is FDA approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndrome (MDS) associated with chromosome 5q deletion with or without additional cytogenetic abnormalities.[9]

There are several possible mechanisms that link the haploinsufficiency molecular lesions with lenalidomide sensitivity.[4][10]

## Prognosis[edit | edit source]

Most affected people have a stable clinical course but are often transfusion dependent.[citation needed]

## References[edit | edit source]

1. ↑ Lazjuk GI; Lurie IW; Kirillova IA; et al. (August 1985). "Partial trisomy 5q and partial monosomy 5q within the same family". Clin. Genet. 28 (2): 122–9. doi:10.1111/j.1399-0004.1985.tb00371.x. PMID 4042393. S2CID 33815922.
2. ↑ Naeim, Faramarz; Rao, P. Nagesh; W. Grody, Wayne (2008). Chapter 8 - Myelodysplastic Syndromes in Hematopathology Morphology, Immunophenotype, Cytogenetics and Molecular Approaches. pp. 129–154. doi:10.1016/B978-0-12-370607-2.00008-9.
3. ↑ Ebert BL; Pretz J; Bosco J; et al. (January 2008). "Identification of RPS14 as a 5q- syndrome gene by RNA interference screen" (PDF). Nature. 451 (7176): 335–9. Bibcode:2008Natur.451..335E. doi:10.1038/nature06494. PMC 3771855. PMID 18202658. Archived (PDF) from the original on 2021-11-18. Retrieved 2021-11-20.
4. ↑ 4.0 4.1 4.2 4.3 Nakhoul H, Ke J, Zhou X, et al. (2014). "Ribosomopathies: Mechanisms of disease". Clinical Medicine Insights: Blood Disorders. 7: 7–16. doi:10.4137/CMBD.S16952. PMC 4251057. PMID 25512719.
5. ↑ Starczynowski DT; Kuchenbauer F; Argiropoulos B; et al. (January 2010). "Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype". Nature Medicine. 16 (1): 49–58. doi:10.1038/nm.2054. PMID 19898489. S2CID 7987486.
6. ↑ Online Mendelian Inheritance in Man (OMIM): 5q- syndrome - 153550
7. ↑ "5q- syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 21 November 2021. Retrieved 4 January 2022.
8. ↑ List A; Dewald G; Bennett J; et al. (October 2006). "Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion". N. Engl. J. Med. 355 (14): 1456–65. doi:10.1056/NEJMoa061292. PMID 17021321.
9. ↑ Raza, A; Reeves, J. A.; Feldman, E. J.; Dewald, G. W.; Bennett, J. M.; Deeg, H. J.; Dreisbach, L; Schiffer, C. A.; Stone, R. M.; Greenberg, P. L.; Curtin, P. T.; Klimek, V. M.; Shammo, J. M.; Thomas, D; Knight, R. D.; Schmidt, M; Wride, K; Zeldis, J. B.; List, A. F. (2008). "Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q". Blood. 111 (1): 86–93. doi:10.1182/blood-2007-01-068833. PMID 17893227.
10. ↑ Voutsadakis IA; Cairoli A (2012) (2012). "A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q – myelodysplastic syndromes". Leukemia & Lymphoma. 53 (5): 779–88. doi:10.3109/10428194.2011.623255. PMID 21955212. S2CID 38251104.

## External links[edit | edit source]

* 5q- syndrome at NIH's Office of Rare Diseases

Classification|

* ICD-O: M9986/3
* OMIM: 153550
* DiseasesDB: 34573

|

* v
* t
* e

Chromosome abnormalities

Autosomal|

| Trisomies/Tetrasomies|

* Patau syndrome
* 13
* Edwards syndrome
* 18
* Down syndrome
* 21

* Warkany syndrome 2
* 8
* Trisomy 9
* Tetrasomy 9p
* Trisomy 16
* Cat eye syndrome/Trisomy 22
* 22

|

Monosomies/deletions|

* (1q21.1 copy number variations/1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome/1p36 deletion syndrome)
* 1
* Wolf–Hirschhorn syndrome
* 4
* Cri du chat syndrome/Chromosome 5q deletion syndrome
* 5
* Williams syndrome
* 7
* Jacobsen syndrome
* 11
* Miller–Dieker syndrome/Smith–Magenis syndrome/17q12 microdeletion syndrome
* 17
* DiGeorge syndrome
* 22
* 22q11.2 distal deletion syndrome
* 22
* 22q13 deletion syndrome
* 22

* genomic imprinting
* Angelman syndrome/Prader–Willi syndrome (15)

* Distal 18q-/Proximal 18q-

X/Y linked|

| Monosomy|

* Turner syndrome (45,X)

|

Trisomy/tetrasomy,
other karyotypes/mosaics|

* Klinefelter syndrome (47,XXY)
* XXYY syndrome (48,XXYY)
* XXXY syndrome (48,XXXY)
* XXXXY syndrome (49,XXXXY)

* Trisomy X (47,XXX)
* Tetrasomy X (48,XXXX)
* Pentasomy X (49,XXXXX)

* XYY syndrome (47,XYY)
* XYYY syndrome (48,XYYY)
* XYYYY syndrome (49,XYYYY)

* 45,X/46,XY
* 46,XX/46,XY

Translocations|

| Leukemia/lymphoma|

| Lymphoid|

* Burkitt's lymphoma t(8 MYC;14 IGH)
* Follicular lymphoma t(14 IGH;18 BCL2)
* Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH)
* Anaplastic large-cell lymphoma  t(2 ALK;5 NPM1)
* Acute lymphoblastic leukemia

|

Myeloid|

* Philadelphia chromosome t(9 ABL; 22 BCR)
* Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1)
* Acute promyelocytic leukemia t(15 PML,17 RARA)
* Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1)

Other|

* Ewing's sarcoma t(11 FLI1; 22 EWS)
* Synovial sarcoma t(x SYT;18 SSX)
* Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB)
* Myxoid liposarcoma t(12 DDIT3; 16 FUS)
* Desmoplastic small-round-cell tumor t(11 WT1; 22 EWS)
* Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1)

Other|

* Fragile X syndrome
* Uniparental disomy
* XX male syndrome/46,XX testicular disorders of sex development
* Marker chromosome
* Ring chromosome
* 6; 9; 14; 15; 18; 20; 21, 22

* v
* t
* e

Myeloid-related hematological malignancy

CFU-GM/
and other granulocytes|

| CFU-GM|

| Myelocyte|

| AML:|

* Acute myeloblastic leukemia
* M0
* M1
* M2
* APL/M3

|

MP|

* Chronic neutrophilic leukemia

Monocyte|

| AML|

* AMoL/M5
* Myeloid dendritic cell leukemia

|

CML|

* Philadelphia chromosome
* Accelerated phase chronic myelogenous leukemia

Myelomonocyte|

| AML|

* M4

|

MD-MP|

* Juvenile myelomonocytic leukemia
* Chronic myelomonocytic leukemia

Other|

* Histiocytosis

CFU-Baso|

| AML|

* Acute basophilic

|

CFU-Eos|

| AML|

* Acute eosinophilic

|

MP|

* Chronic eosinophilic leukemia/Hypereosinophilic syndrome

MEP|

| CFU-Meg|

| MP|

* Essential thrombocythemia

* Acute megakaryoblastic leukemia

|

CFU-E|

| AML|

* Erythroleukemia/M6

|

MP|

* Polycythemia vera

MD|

* Refractory anemia
* Refractory anemia with excess of blasts
* Chromosome 5q deletion syndrome
* Sideroblastic anemia
* Paroxysmal nocturnal hemoglobinuria
* Refractory cytopenia with multilineage dysplasia

CFU-Mast|

| Mastocytoma|

* Mast cell leukemia
* Mast cell sarcoma
* Systemic mastocytosis

|

Mastocytosis:|

* Diffuse cutaneous mastocytosis
* Erythrodermic mastocytosis
* Adult type of generalized eruption of cutaneous mastocytosis
* Urticaria pigmentosa
* Mast cell sarcoma
* Solitary mastocytoma

Systemic mastocytosis|

* Xanthelasmoidal mastocytosis

Multiple/unknown|

| AML|

* Acute panmyelosis with myelofibrosis
* Myeloid sarcoma

|

MP|

* Primary myelofibrosis
* Biphenotypic acute leukaemia

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