| ICD-Topo |
C420,C421,C424 |
| ICD-Morpho |
9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
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| ICD-Morpho |
9945/3 Chronic myelomonocytic leukaemia
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| ICD-Morpho |
9873/3 AML without maturation
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| ICD-Morpho |
9874/3 AML with maturation
|
| ICD-Morpho |
9867/3 Acute myelomonocytic leukaemia
|
| Atlas_Id |
1169 |
| Note |
Included are patients with 1q21-25 breakpoints and confirmed NUP98 rearrangement. |
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Figure 1. Partial karyotypes with t(1;11)(q24;p15) (A). Fluorescence in situ hybridization with SureFISH NUP98 probe revealing rearrangement of the gene on metaphase and interphase cells (B) |
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| Disease |
Acute myeloid leukemia (AML), probably treatment related and chronic myeloid leukemia (CML) in progression. |
| Etiology | Acute myeloid leukemia in 4: 2 patients with AML with maturation (AML-M2), in 1 of them that developed 3 years after the start of chemotherapy (MACOP-B) for stage III non-Hodgkin lymphoma (NHL)(immunoblast type) (Nakamura et al., 1999; Hatano et al., 2000) and in the other it was diagnosed 3 years after chemotherapy (ifosfamide, adriamycin, cytoxan, etopside) and radiotherapy for sarcoma of the testis (Soares et al., 2006). 1 patient was diagnosed with AML with minimal maturation (AML-M1) who received chemotherapy (adriamycin, cytoxan, 5-FU) and bone marrow transplantation for breast adenocarcinoma (Kobzev et al., 2004), 1 with myelodysplastic syndrome evolving into acute myelomonocytic leukemia (M4) that developed after chemotherapy (doxorubicin, ifosfamide) and radiotherapy for liposarcoma with the latency period from chemotherapy to the onset of MDS (treated with azacytidine) 30 months and of AML 38 months (Zhang et al., 2007). 2 patients had CML in transformation, 1 of them on hydrea and myleran therapy (Kobzev et al., 2004) and the other received hydroxyurea during the chronic phase and chemotherapy (arabinosylcytosine, aclamycin, daunarubicin) during transformation that developed after 2.5 years of chronic phase (Bai et al., 2006). Our unpublished case received chemotherapy (MECOB-P) for B-cell NHL and developed chronic myelomonocytic leukemia (CMML) 18 month later. |
| Epidemiology | 5 patients with confirmed NUP98 rearrangement (4 males and 1 female aged 42 to 74 years, median 51 years) (Hatano et al., 2000 Kobzev et al., 2004; Bai et al., 2006; Zhang et al., 2007) and an 18 years old male without molecular studies (Soares et al., 2006). NUP98 rearrangement was also detected in a 36 years old male (unpublished data). |
| Evolution | In 1 AML-M2 patient, complete remission of leukemia was achieved, but the NHL relapsed and an advanced gastric carcinoma was found and the patient died shortly afterwards (Hatano et al., 2000) and the other patient with AML-M2 died 5 months after leukemia onset (Soares et al., 2006). The 2 other AML patients died shortly after the onset of leukemia (Kobzev et al., 2004; Zhang et al., 2007) as well as the patient with CML in transformation (Kobzev et al., 2004). From these data it appears that the clinical course of patients is quite aggressive and the prognosis is dismal. |
| Cytogenetics Morphological | Patients had variable breakpoints assigned to chromosome 1q, but FISH and/or molecular studies confirmed the involvement of PRRX1 that is mapped to 1q24.2, therefore chromosome 1 breakpoints in patients were the same. |
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Figure 2. Karyotype of our unpublished case with t(1;11)(q24;p15) (arrows). |
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| Additional anomalies | Sole anomaly in 1 AML (Kobzev et al., 2004) and in 1 patient during the MDS phase (Zhang et al., 2007); found in association with limited anomalies in the remaining AML patients: +8 (Zhang et al., 2007) and del(7q)/+8 subsequently acquired during MDS progression (Zhang et al., 2007). Sole additional anomaly to t(9;22)(q34;q11) in both progressed CML patients (Kobzev et al., 2004; Bai et al., 2006); found as the only karyotypic anomaly in our unpublished case. |
| Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats |
| Bai XT, Gu BW, Yin T, Niu C, Xi XD, Zhang J, Chen Z, Chen SJ |
| Cancer Res 2006 May 1;66(9):4584-90 |
| PMID 16651408 |
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| Translocation (1;11)(q23;p15), a novel simple variant of translocation (7;11)(p15;p15), in a patient with AML (M2) accompanied by non-Hodgkin lymphoma and gastric cancer |
| Hatano Y, Miura I, Kume M, Miura AB |
| Cancer Genet Cytogenet 2000 Feb;117(1):19-23 |
| PMID 10700860 |
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| Analysis of translocations that involve the NUP98 gene in patients with 11p15 chromosomal rearrangements |
| Kobzev YN, Martinez-Climent J, Lee S, Chen J, Rowley JD |
| Genes Chromosomes Cancer 2004 Dec;41(4):339-52 |
| PMID 15390187 |
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| NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15) |
| Nakamura T, Yamazaki Y, Hatano Y, Miura I |
| Blood 1999 Jul 15;94(2):741-7 |
| PMID 10397741 |
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| Secondary acute myeloid leukemia with a t(1;11)(q23;p15) in an adolescent treated for testicular sarcoma |
| Soares EM, Santos N, de Araújo Silva Amaral B, Silva ML, Leite EP, Silva MO, Muniz MT, Ribeiro RC, de Morais VL, de Jesus Marques Salles T |
| Cancer Genet Cytogenet 2006 Aug;169(1):83-5 |
| PMID 16875945 |
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| Rare t(1;11)(q23;p15) in therapy-related myelodysplastic syndrome evolving into acute myelomonocytic leukemia: a case report and review of the literature |
| Zhang L, Alsabeh R, Mecucci C, La Starza R, Gorello P, Lee S, Lill M, Schreck R |
| Cancer Genet Cytogenet 2007 Oct 1;178(1):42-8 |
| PMID 17889707 |
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