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.     

Additional acquisition of t(1;21)(p32;q22) in a patient relapsing with acute myelogenous leukemia with NUP98-HOXA9

We report a 29-year-old Japanese male with acute myelogenous leukemia (AML)-M4 with a cryptic t(7;11)(p15;p15), in which a chimeric NUP98-HOXA9 fusion was detected by polymerase chain reaction analysis and a chromosomal analysis showed 46,XY. The patient received intensive chemotherapy and underwent autologous stem cell transplantation, and remission was confirmed by the disappearance of NUP98-HOXA9. However, 6 months after transplantation, the patient relapsed; NUP98-HOXA9 was detected again and karyotypic analysis revealed 46,XY, t(1;21)(p32;q22). Fluorescent in situ hybridization (FISH) analysis using an AML1-ETO translocation dual probe, showed that the 21q22 breakpoint involved AML1 locus. A retrospective FISH analysis showed that t(1;21) was absent at onset. This is the first reported case with AML who had a cryptic t(7;11)(p15;p15), and additionally acquired t(1;21)(p32;q22) at relapse.     

Juvenile myelomonocytic leukemia with t(7;11)(p15;p15) and NUP98‐HOXA11 fusion

The t(7;11)(p15;p15) translocation has been reported as a rare and recurrent chromosomal abnormality in acute myeloid leukemia (AML) patients. The NUP98‐HOXA9 fusion gene with t(7;11)(p15;p15) was identified and revealed to be essential for leukemogenesis and myeloproliferative disease. To date, t(7;11)(p15;p15) with NUP98‐HOXA11 fusion has been reported only in one case of ph‐negative chronic myeloid leukemia (CML). Here, we report a case of a 3‐year‐old girl with juvenile myelomonocytic leukemia (JMML) carrying t(7;11)(p15;p15) abnormality with NUP98‐HOXA11 fusion. AML chemotherapy followed by bone marrow transplantation (BMT) was found to be effective in treating this disorder, and she remains in complete remission for 3 years after BMT. We suggest the possibility that AML chemotherapy might be effective for treating JMML with t(7;11)(p15;p15) abnormality and NUP98‐HOXA11 fusion. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Establishment of a myeloid leukaemia cell line (Kasumi-4) with t(9;22;11)(q34;q11;q13), inv(3)(q21q26) and the EVI1 gene activation from a patient with chronic myelogenous leukaemia in blast crisis

A novel human leukaemia cell line (Kasumi-4) was established from the peripheral blood of a 6-year-old girl suffering from chronic myelogenous leukaemia (CML) in blast crisis. The Kasumi-4 cells had the following characteristic features: undifferentiated blasts which were positive for CD34, CD33 and CD13 surface markers, but negative for myeloperoxidase platelet peroxidase, CD36, CD41 and CD42; chromosome abnormalities of t(9;22;11) (q34;q11;q13), inv(3)(q21q26); and elevated expression of EVI1 gene which is located at chromosome band 3q26. Megakaryocytic maturation was not observed in the liquid culture following the addition of TPA, IL-3, IL-6 or GM-CSF. b2-a2 type of BCR-ABL chimaeric messenger RNA was detected by RT-PCR analysis. This is the first leukaemia cell line with a three-way translocation containing the Ph chromosome and the second cell line with an inv(3)(q21q26). This cell line appears to be useful for studying the mechanisms of leukaemogenesis involving these chromosomal abnormalities and related oncogenes.     

Acute myeloid leukaemia with t(8;16)(p11;p13) in a child after intrauterine X-ray exposure

We describe t(8;16)(p11;p13) acute myeloid leukaemia (AML-M4) in a 12-year-old white male with a history of prenatal X-ray exposure. He had skin and bone involvement and some of the leukaemic blasts showed haemophagocytosis, characteristic features seen in t(8;16) AML. 20% of the reported cases of t(8;16)(p11;p13) AML are therapy-related and this case further supports the possible role of the ionizing radiation in the development of this disorder.     

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.     

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.     

Acute myeloid leukaemia with t(9;11)(p22;q23) in a patient treated for adult T cell leukaemia

A 37-year-old male patient with adult T cell leukaemia (ATL) began receiving chemotherapy in March 1992. He achieved complete remission in May 1992, but developed acute myeloid leukaemia (AML, FAB subtype M2) with t(9;11)(p22;q23) in May 1993. The presence of chromosome 11 abnormality at band 11q23 in this patient suggests that the AML was related to the chemotherapy with etoposide for ATL. Furthermore, the combination of etoposide with two cytostatic drugs, cyclophosphamide and carboplatin, possibly induced the leukaemia early (14 months) after the start of chemotherapy. To our knowledge, this is the first report of therapy-related AML after chemotherapy for ATL.     

Chronic myelomonocytic leukaemia with t(8;9)(p11;q34) in childhood: an example of the 8p11 myeloproliferative disorder?

We describe the case of a 10-year-old girl with chronic myelomonocytic leukaemia with the chromosomal translocation t(8;9)(p11;q34), who had developed tonsillar lymphoma as extramedullary involvement at the initial presentation. The cytogenetic study of the cells in both bone marrow and tonsils demonstrated t(8;9)(p11;q34), despite no malignant features in the bone marrow specimens. She developed acute leukaemic transformation 8 months after diagnosis during chemotherapy for lymphoma. Although etoposide reduced the number of blasts, t(8;9)(p11;q34)-bearing cells were not eradicated. Complete remission was obtained following an unrelated bone marrow transplantation. The clinical characteristics of this patient are similar to those of the patients with t(8;9)(p11;q34 or q32) or t(8;13)(p11;q11 or q12) reported previously. The unusual progression of the disease might be associated with the presence of t(8;9)(p11;q34), suggesting a part in the 8p11 myeloproliferative syndrome.