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CASE REPORTS in HAEMATOLOGY
(Paper co-edited with the European LeukemiaNet)
A case of sole i(4)(p10) in myelodysplastic syndrome
 
Written2013-07François 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)
Clinics
Age and sex : 79 year(s) old male patient.
Previous History : no preleukemia
The patient had an acute myeloid leukemia (AML) of unknown type, 20 years ago
no inborn condition of note
Organomegaly : no hepatomegaly ; no splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement
Blood
WBC : 2.7 x 109/L ; Hb : 9.7 g/dL ; platelets : 73 x 109/L;
Bone marrow : hypercellullar, multilineage dysplasia: 13% blasts, no Auer rods, 12% ring sideroblasts, 4% basophils
Cyto pathology classification
Cytology : Refractory anemia with excess blasts (RAEB)
Precise diagnosis : RAEB2 (WHO 2008)
Survival
Date of diagnosis: 01-2013
Treatment : Azacytidine. Blood transfusions were no more needed since.
Complete remission : None
Treatment related death : -
Relapse : -
Status : Alive
Survival : 4 month(s)
Karyotype
Sample : Bone marrow ; culture time : 24 h ; banding : BHG
Results : 47,XY,+i(4)(p10).ish i(4)(p10)(FRGFR3++, wcp4+)[12] / 47,XY,+8[1]
Other molecular cytogenetics technics : FISH. probe cytocell: FGFR3/IGH; ERG1; RELN/TES; ETO/AML1 (RUNX1T1/RUNX1). probe Q-Biogene: wcp4.
Other molecular cytogenetics 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]
Figure 1: RHG; partial panel of chromosomes 4 and i(4)(p10).
Figure 2: one metaphase labelled by wcp4: two normal chromosomes 4 and one extra derived chromosome 4.
Figure 3: nuc ish(FGFR3x4,IGHx2); FGFR3 red and IGH green.
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
We present a new case of isochromosome 4p in a myeloid proliferation. The patient, a 79 years old man developed an MDS (RAEB2), occurring 20 years after an acute myeloid leukemia not otherwise documented. Cytogenetics on bone marrow aspirate revealed a unique abnormality in the karyotype, an additional isochromosome 4p. FISH with wpc4 and FGFR3 probes confirmed the i(4p) as an extra chromosome. The most frequent molecular/cytogenetic abnormalities in myeloid proliferations were absent: 5q31, 7q22-q31 probes (for del 5q or del 7q) and ETO + AML1 probes (for +8 or +21) showed no abnormality.
To our knowledge, this is the sixth reported case of myeloid proliferation with an isochromosome 4p as the sole karyotype abnormality. The previous published cases were M4-AML (3 cases), M2-AML (1 case) and RAEB-T (1 case) (Hagemeijer et al., 1981; Hoo et al., 1995; Chen et al., 1999; Soriani et al., 2010). In this short series, only one relapse is recorded after 9 months, it is the unique case of double i(4p); two cases are noted as being in complete remission and two are not documented. The present case is not relevant to the prognosis value of this karyotype anomaly: first, to date the duration of treatment is only three months, but also the age of the patient, and a previous history of AML are factors which impact the prognosis too greatly by themselves. Isochromosome 4p currently does not have a specific prognostic value in myeloid proliferations.
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 collaboration
francoisdesangles@hotmail.com
Internal links
Atlas Cardi(4p)
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