del(5q) in myeloid malignancies

Identity

Note	Interstitial del(5q) was first described in refractory anaemia; it is also the most common structural rearrangement in myelodysplastic syndromes (MDS) and in acute myeloid leukemias (ANLL); del (5q) is accompanied with given clinical and haematological features; we herein summarize these three pictures as: 1- "the 5q- syndrome", with del(5q) as the sole karyotypic anomaly, 2- MDS with del(5q) and additional karyotypic anomalies, and 3- ANLL with del(5q) (solely or not).
	del(5fq) G-banding (top) - Courtesy Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at theWaisman Center (left and middle) and Jean-Luc Lai (right); R-banding (bottom), Editor (left) del(5)(q21q34) and Courtesy Christiane Charrin (middle and right)

Clinics and Pathology

Disease	1- the 5q- syndrome is a myelodysplastic syndrome
Phenotype / cell stem origin	classified as refractory anemia (RA) in 75% of cases, RA with excess blasts (RAEB) in 15%.
Etiology	possibility of a toxic agent in the environment
Epidemiology	mean age 65-70 yrs; sex ratio: 1M/3F.
Clinics	blood data: macrocytic anemia, minor leukopenia, normal or high thrombocytosis.
Cytology	bone marrow erythroid hypoplasia (50%) and characteristic hypolobulated megakaryocytes (95%).
Treatment	supportive treatment requiring regular blood transfusions for years, leading patients to develop clinical symptoms of iron overload
Prognosis	favorable, with a low risk of transformation in acute leukemia (15%); median survival is 5 yrs.

Disease	2- MDS with del(5q) and additional karyotypic anomalies are de novo and therapy-related MDS
Phenotype / cell stem origin	classified as RAEB or RAEB in leukemic transformation (RAEBT), chronic myelomonocytic leukemia (CMML) in transformation (rare)
Etiology	of therapy-related MDS: prior exposure to alkylating agents with or without radiotherapy
Epidemiology	10-15% of MDS; female preponderance is less characteristic than in above; mean age 65 yrs
Clinics	blood data: macrocytic anemia, leukopenia and low platelet count (50%)
Prognosis	unfavorable; median survival: 10-12 mths

Disease	3- ANLL with del(5q) solely (in 20-25% of cases) or not
Phenotype / cell stem origin	de novo and therapy-related ANLL; all FAB subgroups, mainly M2 ANLL
Etiology	represents 15% of therapy-related AML with prior exposure to alkylating agents with or without radiotherapy
Epidemiology	10-25% of ANLL; mean age 65 years; sex ratio: 1M/1F
Clinics	blood data: anaemia, leukopenia or hyperleucocytosis (blasts) and thrombocytopenia
Prognosis	extremely poor; median survival: 3 mths

Cytogenetics

Cytogenetics Morphological

del(5q) is an interstitial deletion with variable proximal and distal breakpoints, and all the 13 bands between 5q11 and 5q35 have been implicated as breakpoints in MDS and ANLL; the more frequently reported breakpoints are 5q12-14 (proximal) and 5q31-33 (distal); a common segment within 5q31 is deleted in all cases; del(5)(q13.3q33.1) is the most common rearrangement, and is observed in all cases of 5q- syndrome which represent a distinct clinical subgroup (see above).

Additional anomalies

monosomy 7, trisomy 8, monosomy 17p or other chromosomal defects are frequently associated with del(5q) in ANLL, leading to complex karyotypes; in such cases, it is not possible to know whether del(5q) is the primary event; unbalanced translocations involving 5q14-5q34 deletion are occasionaly reported and frequently associated with complex karyotype; identification of chromosome partners implicated in these translocations is often arduous and requires both standard R and G banding, and FISH techniques (chromosome painting).

Genes involved and Proteins

Note

del(5q) results in genetic event(s) which lead to loss of heterozygosity from chromosome 5, suggesting that tumor suppressor genes, important for the development of MDS and/or ANLL may be located in the deleted region; the smallest deleted region is an approximately 5 Mb region located in 5q31 band; molecular genetic and FISH techniques using panels of ordered DNA markers have been used and allowed to map this critical region: the three candidate genes on which most interest has focused are EGR1 (early growth response 1 protein) , IRF1 (interferon regulatory factor 1), and CSF1R (CSF1 receptor)

External links

Other database	del(5q) in myeloid malignancies	Mitelman database (CGAP - NCBI)

To be noted

The finding of a del(5q) during course of a myeloproliferative disorder (MPD) suggests a therapy-related process, and, therefore, a complete change in the prognosis

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Contributor(s)

Written	03-1998	Christiane Charrin
		Service d'Hematologie, Hopital Edouard Herriot, Lyon, France

Citation

This paper should be referenced as such :

Charrin C . del(5q) in myeloid malignancies. Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://AtlasGeneticsOncology.org/Anomalies/del5qID1092.html

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