Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis

Ishiyama, Ken; Takami, Akiyoshi; Kanda, Yoshinobu; Nakao, Shinji; Hidaka, Masaaki; Maeda, Takeyasu; Naoe, Tomoki; Taniguchi, Shuichi; Kawa, Keisei; Nagamura, Tokiko; Atsuta, Yoshiko; Sakamaki, Hisashi

doi:10.1038/leu.2011.229

Cited by 19 publications

(22 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The numbers are small and considering the above-mentioned limitations, our results are in accordance with those of other small series. 12,13 Notably, 14 children were transplanted after relapse and it is possible that a potential beneficial effect of HSCT after relapse is reflected in the high salvage rate. HSCT seems beneficial in patients with t(6;9)/DEK-NUP214 and in particular for patients with FLT3-ITD.…”

Section: Discussionmentioning

confidence: 99%

“…1,[5][6][7] Recent smaller studies, including both adult and pediatric patients, have shown that treatment with early allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission may improve the outcome. 1,12,13 The t(6;9) results in a fusion of the 5' part of the DEK gene at 6p22.3 and the 3' part of the NUP214 gene, formerly known as CAN, located at 9q34, forming the chimeric DEK-NUP214 gene.…”

Section: Introductionmentioning

confidence: 99%

“…17 The characteristics of t(6;9)/DEK-NUP214 AML have so far not been separately described in pediatric patients and the prognostic impact in pediatric AML is unclear. 1,12,13,18 The aims of this study were to characterize the clinical, genetic and morphological features of t(6;9)-positive childhood myeloid neoplasms in the largest series so far; to evaluate outcome and to identify genes potentially involved in leukemogenesis of t(6;9) using gene expression profiling.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

et al. 2014

View full text Add to dashboard Cite

IntroductionThe t(6;9)(p22;q34), frequently reported with a breakpoint in 6p23 but now known to involve the DEK gene mapping to 6p22.3, is a rare translocation, estimated to occur in 1-2% of cases of childhood acute myeloid leukemia (AML). 1 The translocation was first identified in 1976, and the first pediatric patient was described in 1982.2,3 The World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia from 2008 listed the t(6;9)(p22;q34) as a distinct entity. 4 However, our current knowledge of t(6;9)(p22;q34) in AML is drawn from relatively small series of patients, predominantly adults, associating t(6;9) with young age at onset and a poor outcome. 1,[5][6][7] Typically, the t(6;9) presents as de novo AML, morphologically associated with FrenchAmerican-British (FAB) type M2, bone marrow basophilia, Auer rods, and dysplasia. 1,5,7,8 The translocation is primarily the sole cytogenetic abnormality (80%); among the 20% of ©2014 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2013 The online version of this article has a Supplementary Appendix. Manuscript received on September 24, 2013. Manuscript accepted on January 13, 2014 Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-AmericanBritish M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

et al. 2014

View full text Add to dashboard Cite

show abstract

“…5 However, 55% of the AML patients with t(6;9)(p23;q34) eventually had a negative outcome. We herein performed a further analysis for AML patients with t(6;9)(p23;q34) who received allo-HSCT to identify the prognostic factors affecting their overall survival (OS).…”

mentioning

confidence: 99%

“…3,4 The detoxification and elimination of xenobiotic compounds is one of the most investigated processes in cancer susceptibility, with several evidences of its association with cancer risk. 5 ATP-binding cassette (ABC) subfamily B, member 1 (ABCB1 or MDR1); subfamily G, member 2 (ABCG2 or BCRP); subfamily C, member 2 (ABCC2 or…”

mentioning

confidence: 99%

Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who underwent an allogeneic hematopoietic stem cell transplant

et al. 2011

Self Cite

View full text Add to dashboard Cite

tions, and the germline sets (A and C) have the advantage of not requiring DNA sequencing or specific custom-made primers.Two DNA MRD markers with high sensitivity (at least 10 À4) are generally required in MRD intervention clinical trials, 1,9 and in a large cohort of 2854 pediatric precursor B ALL patients, 20% of patients had only one sensitive marker and 8% had none.9 Four of the 16 cases evaluated in this study had only one sensitive Ig/TCR marker so that availability of IKZF1-based MRD testing would have been useful for their risk stratification. Using routine PCR, IKZF1D3 --6 rearrangements were identified in 6% of ALL patients in the ANZCHOG cohort in this study, so inclusion of this marker in standard screening for MRD targets would be an easy way to provide more patients with two sensitive markers.The concept of using disease-related markers for MRD testing has been already established for fusion transcripts such as BCR-ABL and for gene rearrangements such as for SIL-TAL1 in T-ALL and for MLL rearrangements in infant ALLs.10 Kuiper et al. 4 in an analysis of paired diagnosis and relapse samples from 34 patients found IKZF1 deletions and nonsense mutations in 14 (41%) patients at diagnosis and showed that all were conserved at relapse, in contrast to other recurrent genetic lesions found at diagnosis such as PAX5, CDKN2A and EBF1. It is therefore likely that this IKZF1 marker will be at least as stable as Ig/TCR rearrangements, although this will need to be confirmed in more extensive studies.In summary, we have assessed three ways to measure MRD levels by RQ-PCR for the most common deletion of the IKZF1 gene found in ALL and demonstrated that all three methods provided robust and sensitive MRD assays for patients with this arrangement. The two primer and probe sets based on germline sequences could be used within a few days of diagnosis to provide quantitative measures of very-early responses to therapy. We expect that IKZF1 gene deletions (IKZF1D3 --6 and probably others) will provide a useful addition to the repertoire of MRD markers currently available for monitoring MRD in ALL.

show abstract

Acute myeloid leukemia

Johansson

Harrison

2015

Cancer Cytogenetics

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis

Cited by 19 publications

References 12 publications

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who underwent an allogeneic hematopoietic stem cell transplant

Acute myeloid leukemia

Contact Info

Product

Resources

About