t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia

Two cases of T acute lymphoblastic leukaemia (T-ALL) with an identical t(4;11)(q21;p15) translocation were identified within a prospective study on the biological and clinical features of adult ALL patients enrolled into the therapeutic protocol ALL0496 of the GIMEMA Italian Group. In both cases, the molecular characterization showed an involvement of the NUP98 gene on 11p15 which rearranges with the RAP1GDS1 gene on 4q21. The morphological and immunological features of the leukaemic cells, as well as the clinical behaviour and response to induction therapy, were the same in both patients. Based on the available data, the t(4;11)(q21;p15) translocation involving the NUP98-RAP1GDS1 fusion gene emerges as a new highly specific genetic abnormality that characterizes a subset of T-ALL.     

t(7;11)(p15;p15) Chronic myeloid leukaemia developed into blastic transformation showing a novel NUP98/HOXA11 fusion

We encountered a patient with Philadelphia-negative chronic myeloid leukaemia, with t(7;11)(p15;p15), in whom acute leukaemia phase (acute myeloid leukaemia-M2 morphology) developed within a short period. We detected a novel gene fusion between NUP98 and HOXA11 both in the chronic phase and in the acute leukaemia phase in this case. Although it is well known that a fusion of NUP98-HOXA9 in myeloid malignancies is created by the t(7;11)(p15;p15), this case suggests the possibility that HOXA11 might be another partner gene for NUP98 in t(7;11)(p15;p15) leukaemia.     

Molecular cloning of the breakpoint of t(11;22)(q23;q11) chromosome translocation in an adult acute myelomonocytic leukaemia

Southern blot analysis with a cDNA probe of MLL indicated that the breakpoint is in a Bam HI 8.3 kb fragment which carries the exon 5–11 of MLL gene in DNA from an adult acute myelomonocytic leukaemia with a t(11;22)(q23;q11) translocation. The structural analysis of the rearranged MLL locus demonstrated that the breakpoint is localized between exon 8 and 9 of MLL locus. The normal counterpart fused to the MLL locus was proved to be derived from chromosome 22q11( AF-22 ) by somatic cell hybrids analysis and FISH. By FISH, AF-22 locus was localized to the region more centromeric to the BCR gene.     

Involvement of the NUP98 Gene in a Chromosomal Translocation t(11;20)(p15;q11.2) in a Patient With Acute Monocytic Leukemia (FAB-M5b)

We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia.     

伴t(5;12)(q31;p13),FIP1L1/PDGFRα阴性慢性嗜酸细胞白血病一例并文献复习

目的 提高对慢性嗜酸细胞白血病(CEL)的认识水平.方法 报告1例伴t(5;12)(q31;p13),FIP1样基因1(FIP1L1)血小板衍化生长因子(PDGFRα)(-)CEL的诊治过程.外周血及胸腔积液细胞的免疫表型采用流式细胞术(FCM)分析,染色体采用G显带分析,FIP1L1/PDGFRα融合基因表达采用RT-PCR技术检测,骨髓、肺及脾组织行常规病理学检查.结果 1例16岁女性患者严重贫血、发热、脾大、血小板减少、嗜酸细胞显著增高,持续22个月.骨髓嗜酸细胞浸润伴纤维化改变;肺和脾组织均呈嗜酸细胞浸润,伴脾栓塞.克隆性染色体异常为t(5;12)(q31;p13),不表达FIP1L1/PDGFRα融合基因.外周血及胸腔积液细胞中除大量嗜酸细胞外,CD3-、CD4-、CD8+异常T淋巴细胞分别占淋巴细胞总数的5.43%和1.66%.患者对羟基脲、泼尼松、干扰素和甲磺酸伊马替尼(400 ms/d共40 d)治疗无效,小剂量阿糖胞苷、米托蒽醌、长春新碱、环磷酰胺、甲氨蝶呤、泼尼松等联合化疗仅有短期效果.患者最终死于心、肺、肝、肾多脏器功能衰竭.结论 本例FIP1L1/PDGFRα(-)CEL符合WHO诊断标准,对多种药物及甲磺酸伊马替尼治疗无效,应在疾病早期尽早争取造血干细胞移植.CD3-、CD4-、CD8+克隆性T细胞异常与CEL发病的关系值得关注.     

Acute Myelomonocytic Leukemia with Dysplastic Bone Marrow Eosinophils Showing t(5;17)(q13;q11) and a Secondary Chromosomal Aberration, inv(16)(p13q22)

inv(16)(p13q22) is associated with de novo acute myelomonocytic leukemia with dysplastic bone marrow eosinophils (AMML Eo), which has a relatively favorable clinical course with a longer remission duration and better survival prospects. On the other hand, t(5; 17)(q13;q11), although relatively rare, has been reported to be a component of complex chromosomal abnormalities in myelodysplastic syndromes and secondary acute myeloid leukemia (AML). We treated a 29-year-old woman with the first reported case of de novo AMML Eo with inv(16)(p13q22) in addition to t(5; 17)(q13;q11). Although she attained complete remission (CR) immediately after induction therapy, the disease recurred 1 year after the completion of consolidation therapies. She underwent HLA-matched unrelated allogeneic bone marrow transplantation (UBMT), together with a myeloablative conditioning regimen, after achieving a second CR and has survived without a recurrence for more than 24 months since UBMT. In general, certain secondary chromosomal abnormalities are associated with the phenotype of the disease, which retains its essential biologic characteristics established by the primary abnormality. Accordingly, the primary nature of the leukemic cells in this case differs from the findings for core-binding factor AML with inv(16)(p13q22). We believe this report is the first of de novo AMML Eo with t(5; 17)(q13;q11) showing as a secondary chromosomal aberration with inv(16)(p13q22).     

Multiple myeloma and the translocation t(11;14)(q13;q32): a report on 13 cases

Complex cytogenetic abnormalities have been described in patients with multiple myeloma (MM). To better understand the significance of the most frequent translocation observed in MM, we studied the clinical characteristics of patients with MM and the t(11;14)(q13;q32) abnormality. A search of the cytogenetic database at the Mayo Clinic identified patients with MM and t(11;14)(q13;q32). The medical records were reviewed for the clinical characteristics of these patients. We identified 13 patients with MM and t(11;14)(q13;q32) determined by standard cytogenetic analysis; in 10 patients the abnormality was detected at the time of relapse (three with previously normal results of cytogenetic examination). At the time the translocation was detected, plasma cell (PC) leukaemia was clinically diagnosed in two patients. The median number of circulating PCs, as determined by the cytoplasmic immunofluorescence of T-cell-depleted peripheral blood mononuclear cells, was 1.1 × 10⁹/l (mean 1.74; range 0.0017–6.26 × 10⁹/l). On linear regression analysis there was a strong correlation between the number of circulating PCs and the number of bone marrow PCs. The median survival after demonstration of the translocation was 8.1 months. Of all patients, 10 died of disease progression and three were alive. Patients with MM who have t(11;14)(q13;q32) seem to have an aggressive clinical course, even when the abnormality is detected at the time of diagnosis, with evidence of many circulating PCs.     

Acute basophilic leukaemia and translocation t(X;6)(p11;q23)

We report two infants with acute basophilic leukaemia associated with a t(X;6)(p11;q23) as the sole abnormality. Morphologic evidence of basophilic lineage was provided by light and electron microscopy. Both patients also had a similar presentation on diagnosis, characterized by clinical signs consistent with a hyperhistaminaemia syndrome, i.e. urticarian rashes and gastro-intestinal disorders evocative of peptic ulcer. Immunophenotypes differed in the two patients, one expressing CD24, CD13 and CD33, whereas only CD117 was found in the other.
Basophilic acute leukaemia, a rare group among acute leukaemias, might be nonrandomly associated with a specific chromosomal abnormality, t(X;6)(p11;q23). This new entity might also be identifiable by an uncommon clinical presentation and occurrence in infancy.     

A novel translocation t(1;7)(p36;q34) in three patients with acute myeloid leukaemia

Studies of large numbers of patients have enabled the identification of relatively infrequent chromosome changes, such as inv(3)(q21;q26), t(6;9)(p23;q34) and t(8;16)(p11;p11), whose clinico-biological significance is gradually becoming clearer. Translocations involving chromosomes 1 and 7 are relatively rare in myeloid neoplasias, being found in far less than 1% of cases; the rearrangement that occurs most frequently consists of an unbalanced translocation [t(1;7)(p11; p11)], resulting in complete loss of 7q, associated with therapy-related or environmentally-induced high-risk myelodysplasia. We recently observed three cases of acute myeloid leukaemia (AML) with a previously unreported balanced translocation t(1;7) (p36;q34). Case 1 underwent autologous bone marrow transplantation and remains alive in CR; cases 2 and 3 relapsed after 10 and 4 months, respectively. The response to chemotherapy observed in our cases suggests that variable clinical features might be present in the broad cytogenetic category usually referred to as '7q abnormalities' and contributes to an interesting previous observation of prolonged disease-free survival in a subset of AMLs with 7q- as the isolated chromosome change.