A case of sole i(4)(p10) in myelodysplastic syndrome

François Desangles, Aurélie Servonnet, Hubert Nielly, Serge Cremades, Jean-Etienne Pilo  

Laboratoire de Biologie Medicale, HIA Val de Grace, 74bd Port-Royal, F 75005 Paris, France (FD, AS); Medecine - Oncologie, HIA Begin, 69 ave de Paris, F 94160 Saint Mande, France (HN, SC); Laboratoire de Biologie Medicale, HIA Begin, 69 ave de Paris, F 94160 Saint Mande, France (JEP)

Previous history

Preleukaemia
-
Malignant disease
+ The patient had an acute myeloid leukemia (AML) of unknown type, 20 years ago
Inborn condition
-

Clinics case report

Age
79 yrs
Sex
M
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-

Blood data

Wbc
2.7
Hb
9.7
Platelets
73
Blasts
0
Bone marrow
hypercellullar, multilineage dysplasia: 13% blasts, no Auer rods, 12% ring sideroblasts, 4% basophils

Cyto path

Cytology
Refractory anemia with excess blasts (RAEB)
Precise diagnosis
RAEB2 (WHO 2008)

Survival data

Date diagnosis
01-2013
Treatment
Azacytidine. Blood transfusions were no more needed since.
Complete remission
-
Treatment relat death
-
Relapse
-
Status
A
Survival
4

Karyotype

Sample
Bone marrow
Culture time
24
Banding
BHG
Results
47,XY,+i(4)(p10).ish i(4)(p10)(FRGFR3++, wcp4+)[12] / 47,XY,+8[1]
Mol cytogenet technics
FISH. probe cytocell: FGFR3/IGH; ERG1; RELN/TES; ETO/AML1 (RUNX1T1/RUNX1). probe Q-Biogene: wcp4.
Mol cytogenet results
nuc ish 5p15(D5S721,D5S23x2)5q31(ERG1x2)[100] ; nuc ish 7q22(RELNx2)7q31(TESx2)[100] ; nuc ish 8q22(RUNX1T1x2),21q22(RUNX1x2)[100] ; nuc ish 4p16(FGFR3x4),14q32(IGHx2)[40/50] ; ish +i(4)4p16(wcp4+,FGFR3++)[3/3]

Images

Atlas Image
Figure 1: RHG; partial panel of chromosomes 4 and i(4)(p10).
Atlas Image
Figure 2: one metaphase labelled by wcp4: two normal chromosomes 4 and one extra derived chromosome 4.
Atlas Image
Figure 3: nuc ish(FGFR3x4,IGHx2); FGFR3 red and IGH green.
Atlas Image
Figure 4: two normal chromosomes 4 labelled by an FGFR3 red probe, one extra chromosome labelled by an FGFR3 red probes and two normal chromosomes 14 labelled by an IGH green probe.

Comments section

Comments
At the present time, what interpretation of i(4)(p10) can be proposed? "Considering that trisomy 4 as the sole abnormality of karyotype is common anomalies in AML and MDS", Chen et al. (1999) suppose that "amplification of genes on 4p but not on 4q may play a crucial role in the pathogenesis of MDS and AML". Recently, two genes located on chromosome 4 were identified as playing a role in myeloid proliferations. In 2003, Dvorak et al. have described the increased expression of FGFR3 (4p16), a member of the family of tyrosine kinase genes, in myeloid proliferating cells of CML and AML. Furthermore TET2 in 4q24 is a putative tumor suppressor in myeloid proliferations (Delhommeau et al., 2009; Jankowska et al., 2009, Vainchenker et al., 2011). Thus it can be assumed that the presence of a supernumerary isochromosome 4p can increase the expression of FGFR3 in 4p16 without increasing the copy number of the tumor suppressor gene TET2 in 4q24.
Call for collab
francoisdesangles@hotmail.com

Bibliography

Pubmed IDLast YearTitleAuthors
69441531981Cytogenetic follow-up of patients with nonlymphocytic leukemia. II. Acute nonlymphocytic leukemia.Hagemeijer A et al
78895031995Supernumerary isochromosome 4p in ANLL-M4 myelomonocytic type is associated with favorable prognosis.Hoo JJ et al
104849841999A group of previously not recognized cytogenetic abnormalities in myeloid hematological malignancies.Chen Z et al
145621212003Increased expression of fibroblast growth factor receptor 3 in CD34+ BCR-ABL+ cells from patients with chronic myeloid leukemia.Dvorak P et al
194744262009Mutation in TET2 in myeloid cancers.Delhommeau F et al
193722552009Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms.Jankowska AM et al
208635642010Double supernumerary isochromosome 4p in acute myelomonocytic leukemia.Soriani S et al
216533282011New mutations and pathogenesis of myeloproliferative neoplasms.Vainchenker W et al

Citation

François Desangles, Aurélie Servonnet, Hubert Nielly, Serge Cremades, Jean-Etienne Pilo

A case of sole i(4)(p10) in myelodysplastic syndrome

Atlas Genet Cytogenet Oncol Haematol. 2013-07-01

Online version: http://atlasgeneticsoncology.org/case-report/208871/a-case-of-sole-i(4)(p10)-in-myelodysplastic-syndrome