Derivative (1;18)(q10;q10): a recurrent and novel unbalanced translocation involving 1q in myeloid disorders.

We report two cases of hematological malignancies, comprising a case of myelodysplastic syndrome (MDS) that rapidly evolved into acute myeloid leukemia, and a case of myeloproliferative disorder (MPD), in which der(1;18)(q10;q10) was found as the sole acquired karyotypic abnormality. This observation indicates that the unbalanced translocation is a recurrent aberration in myeloid disorders. To the best of our knowledge, centromeric fusion between long arms of chromosomes 1 and 18, leading to a normal chromosome 18 substituted with a der(1;18) chromosome, is novel and has not been described in cancer. Mechanistically, either trisomy 1q or monosomy 18p that results from the translocation may potentially contribute to leukemogenesis. Finally, chromosomes with large constitutive heterochromatin bands such as chromosome 1 may be at risk of centromeric instability and be predisposed to centromeric fusion with other chromosomes.     

Acute myeloid leukemia with t(5;18)(q35;q21).

A case of acute myelocytic leukemia with a translocation (5;18)(q35;q21) is reported. Cytogenetic abnormalities of the long arm of chromosome 5 have long been known to affect hematopoiesis. Although translocations between 5q and other chromosomes have been associated with malignancy, this is the first reported case of a t(5;18) resulting in acute myeloid leukemia. Possible molecular mechanisms underlying the pathogenesis of the disease are discussed.     

Isochromosome (17)(q10) and translocation (4;12)(q12;p13) in a child with acute myeloid leukemia.

Isochromosome 17q is a commonly observed cytogenetic aberration in hematologic malignancies. Isolated isochromosome 17q usually presents as a marker of a chronic myeloid disorder, with a high propensity for transformation into acute nonlymphoblastic leukemia (ANLL). t(4;12)(q11-12;p13) is a recently described translocation, associated with ANLL, predominantly in adults. In this article, we present a case of acute myeloblastic leukemia (AML) in a 14-year-old female in which i(17q) and t(4;12)(q12;p13) were found in the leukemic clone at diagnosis. We briefly review the literature and hypothesize as to the significance of the coexistence of these cytogenetic changes.     

A novel t(11;12)(q23-24;q24) in a case of minimally-differentiated acute myeloid leukemia (AML-M0)

Acute myeloid leukemia with minimal signs of myeloid differentiation (AML-M0) is a recent addition to the FAB group classification. Chromosome data is scarce, but existing reports describe a high incidence of complex karyotypes and myelodysplastic syndrome-like chromosome alterations, while single chromosome translocations have rarely been reported. We describe the case of a 60-year-old woman diagnosed with AML-M0 with a novel translocation t(11;12)(q23-24;q24) as the sole karyotypic marker. Fluorescence in situ hybridization analysis to assess MLL gene splitting did not show rearrangement of this oncogene.     

Translocation (2;7)(p13;q36) in a case of acute nonlymphocytic leukemia evolving from a myelodysplastic syndrome

A case of acute nonlymphocytic leukemia with a new translocation, t(2;7)(p13;q36), as the sole karyotypic abnormality is reported. The patient's leukemia evolved from a cytogenetically normal myelodysplastic syndrome of 4 years' duration. Following treatment the patient entered complete remission with loss of the cytogenetically abnormal clone. Subsequent bone marrow analyses showed recurrence of the myelodysplastic syndrome with a normal karyotype. Although both chromosomes 2 and 7 are known to be involved in nonrandom karyotypic changes in human cancer and leukemia, t(2;7)(p13;q36) has not been reported previously.     

Nonrandom t(1;22)(p12-p13;q13) in acute megakaryocytic malignant proliferation

A case of acute megakaryocytic leukemia (M7) and one of acute myeloid hemopathy affecting megakaryocytic and erythrocytic cell lineages in infants are reported. Both patients had t(1;22)(p12-p13;q13). This translocation was previously observed in a congenital M7 leukemia. These studies suggest that t(1;22) translocation can be nonrandom in M7.     

A t(11;12) 11q23 leukemic breakpoint that disrupts the MLL Gene

Translocations involving 11q23 have been shown to be a consistent finding in human hematopoietic malignancies and in some constitutional abnormalities. The identification of a gene, MLL (myeloid/lymphoid or mixed-lineage leukemia), that spans the breakpoints in four different recurrent 11q23 translocations was recently reported. We describe a rare (11;12)(q23;p13) translocation, observed in leukemic cells from a patient with acute lymphoblastic leukemia, which also disrupts this gene. © 1993 Wiley-Liss, Inc.     

t(14;19)(q32;q13): a recurrent translocation in B-cell precursor acute lymphoblastic leukemia

The recurrent t(14;19)(q32;q13) translocation associated with chronic B-cell lymphoproliferative disorders, such as atypical chronic lymphocytic leukemia, results in the juxtaposition of the IGH@ and BCL3 genes and subsequent overexpression of BCL3. We report six patients with B-cell precursor acute lymphoblastic leukemia who have a cytogenetically identical translocation with different breakpoints at the molecular level. Fluorescence in situ hybridization with locus-specific probes confirmed the involvement of the IGH@ gene but showed that the breakpoint on 19q13 lay outside the region documented in t(14;19)(q32;q13)-positive chronic lymphocytic leukemia. This newly described translocation constitutes a distinct cytogenetic subgroup that is confined to older children and younger adults with B-cell precursor acute lymphoblastic leukemia.     

Idiopathic myelofibrosis in blast transformation with 4;12 and 5;12 translocations and a 7q deletion

A case of a patient who developed a leukemic transformation following an 8.5-year history of idiopathic myelofibrosis (IMF) with myeloid metaplasis is presented. Surface marker analysis identified the blast cells as myeloid in lineage. The karyotype of unstimulated peripheral blood cells was 46,XY,t(4;12)(q26;15),t(5;12)(q13;q24),del(7)(q22). In the literature, the 7q− has a minor association with IMF, and the t(5;12) translocation has been reported in one case of acute nonlymphocytic leukemia, but neither the t(4;12) nor the combination of these three abnormalities has been reported in IMF.     

11q13 is a cytogenetically promiscuous site in hematologic malignancies.

11q13 translocation has been described in mantle cell lymphoma in the form of t(11;14) (q13;q32), with rearrangement and over-expression of the cyclin D1 gene. Recently, an association between 11q13 and acute myeloid leukemia is recognized. We describe the occurrence of 11q13 translocations in both acute leukemias and myelodysplastic syndrome, and suggest that other genetic mechanisms unrelated to cyclin D1 may be involved in the tumorigensis. Furthermore, 11q13 appears to be a cytogenetically promiscuous site involved in reciprocal translocations with different chromosomes in both myeloid and lymphoid malignancies.     

Chronic myeloid leukemia in blast phase associated with t(3;8)(q26;q24)

We previously reported a recurrent t(3;8)(q26;q24) translocation involving EVI1 in five patients with myelodysplastic syndrome or acute myeloid leukemia. Here we report the same structural abnormality in a case of chronic myeloid leukemia in blast phase. The t(3;8)(q26;q24) occurred several months after the initial diagnosis of chronic myeloid leukemia, while the patient was being treated with a tyrosine kinase inhibitor. We confirmed rearrangement of EVI1 by fluorescence in situ hybridization assay using a dual-color break-apart probe set that spans the EVI1 region. Our findings demonstrate that, similar to other recurrent translocations involving 3q26, such as t(3;3) and t(3;21), the t(3;8)(q26;q24) is implicated not only in myelodysplastic syndrome and acute myeloid leukemia, but also in progression of chronic myeloid leukemia. These findings extend the known disease spectrum associated with this cytogenetic aberration.     

Translocation (12;17)(p11-12;q11-12): a recurrent primary rearrangement in acute leukemia.

We identified two patients with acute leukemia in relapse (one lymphoblastic and the other with evidence of mixed lymphoid-myeloid differentiation) with t(12;17)(p12;q11) as the primary karyotypic abnormality. There are six previously reported cases of acute leukemia with an identical or similar translocation. To our knowledge, t(12;17) has not been reported in other forms of neoplasia. A review of these cases suggests that t(12;17) carries a poor prognosis.     

A der(1;15)(q10;q10) is a rare nonrandom whole-arm translocation in patients with acute lymphoblastic leukemia

A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms of chromosomes 1 and 15, has been reported in patients with various conditions, including acute myelogenous leukemia, myelodysplastic syndrome, polycythemia vera, and multiple myeloma. Only 27 cases of unbalanced der(1;15)(q10;q10) have been documented in the literature as single or complexed chromosomal abnormalities in hematological malignancies. Here, we describe two cases of acute lymphoblastic leukemia with der(1;15)(q10;q10), and review the previous reports. Although more case studies are needed, we suggest that der(1;15)(q10;q10) should be considered a nonrandom chromosomal abnormality in hematological malignancies including both lymphoid and myeloid neoplasms.     

Acute myeloid leukemia associated with hemophagocytic syndrome and t(4;7)(q21;q36)

Hemophagocytic syndrome (HS) is a histiocytic reactive process often associated with infections and/or malignancies. Clonal karyotypic abnormalities have been the hallmark of several hematological malignancies and have been shown to be of clinical significance in terms of both diagnosis and prognosis. While there are limited reports of both clonal and nonclonal abnormalities in HS, their clinical significance has not been established. Detection of such clonal abnormalities, as seen in some cases of HS, may indicate the presence of an occult malignant process, even when there is no microscopic evidence of a hematological malignancy. We report a case of HS in a child with clonal t(4;7)(q21;q36) which later progressed to acute myeloid leukemia (AML) with further clonal evolution. Our case strengthens the argument that cytogenetic studies in HS may be important in identifying the underlying occult malignant process.     

Acute mixed lineage leukemia and a t(6;14)(q25;q32) in two adults

Acute mixed lineage leukemia (AMLL) is a rare form of leukemia in which both myeloid and lymphoid markers are present. Few chromosome abnormalities have been identified associated with this form of leukemia. A translocation involving the long arms of chromosomes 6 and 14 was previously described in four young individuals with acute leukemia and in three of these cases the diagnosis was mixed lineage. We identified a translocation involving the same chromosomes in two additional cases of adults with AMLL. The q32 breakpoint on chromosome 14 is shared by all six cases and five out of six cases also share the q25 breakpoint on chromosome 6. The rarity of the t(6;14) and the AMLL suggests a non-random association between these two events. The near cryptic appearance of the translocation might indicate that its occurrence is underestimated.     

Human homeobox gene HOXC13 is the partner of NUP98 in adult acute myeloid leukemia with t(11;12)(p15;q13)

The chimeric gene NUP98/HOXC13 was detected in a patient with a de novo acute myeloid leukemia and a t(11;12)(p15;q13). Fluorescence in situ hybridization with PAC1173K1 identified the breakpoint on 11p15, indicating that the NUP98 gene was involved in the translocation. At 12q13, the breakpoint fell within BAC 578A18, selected for the homeobox C (HOXC) cluster genes. RACE-PCR showed that HOXC13 was the partner gene of NUP98. To date, HOXC13 is the eighth homeobox gene that, as the result of a reciprocal translocation, fuses with NUP98 in myeloid malignancies.     

A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia

Acute monoblastic leukemia is nonrandomly associated with abnormalities involving 11q. Two infants, one a neonate and the other 19 months of age, had the same hitherto undescribed karyotypic abnormality, t(8;16)(p11;p13), associated with acute nonlymphocytic leukemia M5a. The older child had an additional translocation, t(10;11)(q11;p15), but the chromosome arms affected were the opposite to those described in acute nonlymphocytic leukemia M5a of childhood. Therefore, it is postulated that genes involved in monocytic differentiation may be situated on 8p11 or 16p13, as well as on 11q.     

Therapy-related acute myeloid leukemia with eosinophilia,basophilia, t(4;14)(q12;q24) and PDGFRA rearrangement: a case report and review of the literature

The myeloid and lymphoid neoplasms with eosinophilia and PDGFRA gene rearrangements usually show a good response to Imatinib and are typically associated with a normal karyotype, occasionally exhibiting a secondary chromosomal abnormality associated with clonal evolution. Five variant translocations involving PDGFRA have been reported. Here, we report a rare case of therapy-related acute myeloid leukemia with PDGFRA rearrangement after chemotherapy for prior B lymphoblastic leukemia (B-ALL). The patient had a history of BCR-ABL negative, hypodiploid B-ALL in complete remission after chemotherapy. However, 15 months later the patient developed acute myeloid leukemia with rapidly increasing eosinophilia, basophilia and a complex karyotype that included a novel t(4;14)(q12;q24). FIP1L1 was not associated with the PDGFRA rearrangement. The patient had a very aggressive clinical course, and died from the disease shortly after diagnosis. This is the first case of a primary therapy-related myeloid neoplasm with secondary PDGFRA rearrangement. The t(4:14)(q12;q24) is joining the growing list of the variant translocations involving PDGFRA.