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(Paper co-edited with the European LeukemiaNet)
Inversion(11)(p15q22) as a secondary anomaly in a case of relapsed MDS-RAEB after unrelated donor hematopoietic cell transplantation
Written2013-04Yan Zhang, Xinjian Yu, Jinhong Liu
Research Center of Hematology, Fudan University, Shanghai Daopei Hospital, Shanghai, P R China
Age and sex : 38 year(s) old female patient.
Previous History : preleukemia (previous diagnosed as MDS-RAEB, with isolated deletion 20q)
no previous malignant disease
no inborn condition of note
Organomegaly : no hepatomegaly ; no splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement
WBC : 2.58 x 109/L ((neutrophils 36.30% lymphocytes 47% monocytes 13.90%)); Hb : 103 g/dL ; platelets : 42 x 109/L; blasts : 6.59 % .
Bone marrow : 5 the bone marrow was normocellular with 5% myeloblasts, 8% promyelocytes, with dysplasia in myeloid and erythroid lineages
Cyto pathology classification
Immunophenotype : There were 10% myeloid blasts positive for C34, CD117, CD13, CD33, and HLA-DR and partially positive for cMPO.
Precise diagnosis : Relapsed MDS-RAEB 4 months after unrelated donor HCT.
Date of diagnosis: 02-2012
Treatment : Date of the first HCT: 02-2012, a second HCT: 10-2012
Complete remission was obtained
Comments : complete remission 1 month after the first HCT (03-2012)
Treatment related death : died of acute graft versus host disease and serious infection
Relapse : four months after the first HCT (07-2012)
Status : Dead 12-2012
Survival : 10 month(s)
Sample : Bone marrow ; culture time : 24 h ; banding : G banding
Results :
Karyotype at relapse : 46,XX,del(20)(q11.2)[5]/46,XX,inv(11)(p15q22),del(13)(q22q32),add(16)(q22),add(19)(q13.3),del(20)(q11.2) [cp13]/46,XX [2]
Other molecular cytogenetics technics : Karyotype 17 days after the second HCT: 46,XY[30]
Other molecular cytogenetics results : Fluorescence in situ hybridization (FISH) result 17 days after the second HCT (using XY DNA probe): 99.8% XY signal (donor-originated)
Other molecular studies
technics : RT-PCR: Not done because no sample left to extract RNA.
Left: G-banded partial karyogram at relapse, showing the inv(11)(p15q22) and del(20)(q11). Right: FISH result using centromeric XY DNA probe (Vysis) after the second HCT showing 99.8% XY signal (donor-originated).
Table 1. Summary of publicly reported cases with inv(11)(p15q22) and NUP98-DDX10 fusion gene.
Inversion(11)(p15q22) is a rare entity. It has been found as abnormal clone in MDS or myeloid leukemia, either de novo or secondary, in both children and adults. There seems to be male predominance. To our knowledge, this is the first case report that presents inv(11)(p15q22) as an additional cytogenetic abnormality besides deletion 20q, a common aberration in MDS. Previously, Yamamoto M et al reported the appearance of an inv(11)(p15q22) as a secondary anomaly in a chronic myeloid leukemia (CML) patient undergoing treatment with imatinib, suggesting a possibility that this abnormality might be involved in drug resistance and disease evolution.
Our patient was diagnosed as MDS-RAEB with isolated deletion 20q at admission. One month after unrelated donor HCT, the patient reached complete hematologic and cytogenetic remission. However, about four months after transplantation, myeloblasts recurred in the bone marrow. Flow cytometry examination revealed about 10% abnormal cells with characteristic immunophenotype of myeloblasts. Cytogenetical detection revealed two abnormal clones, one with sole deletion 20q, the other with inv(11)(p15q22) and other aberrations besides deletion 20q. We speculate the occurrence of inv(11)(p15q22) with two possibilities: (1) clonal evolution, because the patient had isolated deletion 20q at initial diagnosis, which is common in MDS patients. In general condition, clonal evolution means disease progression and leukemic transformation in MDS, so acquisition of inv(11)(p15q22) might be a cause of relapse after HCT. (2) therapy-related aberration, as the patient received high-dose pretreatment before donor stem cell infusion, although this is unlikely.
Until now 13 cases with inv(11)(p15q22) have been reported by literature review (Table 1). This inversion leads to fusion of DDX10, a putative RNA helicase gene at 11q22 with the nucleoporin gene NUP98 at 11p15. The previously described cases with this chromosome anomaly and NUP98-DDX10 fusion gene comprising 5 children,7 adults and 1 unknown. 8 cases had diagnosis of de novo or secondary AML, 4 cases had primary or therapy-related MDS, and one CML case was found with this chromosome abnormality in acute phase. NUP98-DDX10 fusion, another type of NUP98 rearrangements, might be associated with the poor clinical course.
Internal links
Atlas Cardinv(11)(p15q22)
The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10.
Arai Y, Hosoda F, Kobayashi H, Arai K, Hayashi Y, Kamada N, Kaneko Y, Ohki M.
Blood. 1997 Jun 1;89(11):3936-44.
PMID 9166830
The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts.
Ikeda T, Ikeda K, Sasaki K, Kawakami K, Takahara J.
Int J Hematol. 1999 Apr;69(3):160-4.
PMID 10222653
Cytogenetics in leukemia and its atlas.
Xue YQ.
Tianjin:Tianjin Science and Technology Press,2003.7-12.
Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib-resistant chronic myelogenous leukemia.
Yamamoto M, Kakihana K, Kurosu T, Murakami N, Miura O.
Cancer Genet Cytogenet. 2005 Mar;157(2):104-8.
PMID 15721630
Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence in situ hybridization.
Nebral K, Konig M, Schmidt HH, Lutz D, Sperr WR, Kalwak K, Brugger S, Dworzak MN, Haas OA, Strehl S.
Haematologica. 2005 Jun;90(6):746-52.
PMID 15951287
Inversion (11)(p15q22) with NUP98-DDX10 fusion gene in pediatric acute myeloid leukemia.
Morerio C, Acquila M, Rapella A, Tassano E, Rosanda C, Panarello C.
Cancer Genet Cytogenet. 2006 Dec;171(2):122-5. (REVIEW)
PMID 17116492
NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogenetique Hematologique.
Romana SP, Radford-Weiss I, Ben Abdelali R, Schluth C, Petit A, Dastugue N, Talmant P, Bilhou-Nabera C, Mugneret F, Lafage-Pochitaloff M, Mozziconacci MJ, Andrieu J, Lai JL, Terre C, Rack K, Cornillet-Lefebvre P, Luquet I, Nadal N, Nguyen-Khac F, Perot C, Van den Akker J, Fert-Ferrer S, Cabrol C, Charrin C, Tigaud I, Poirel H, Vekemans M, Bernard OA, Berger R; Groupe Francophone de Cytogenetique Hematologique.
Leukemia. 2006 Apr;20(4):696-706.
PMID 16467868


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