Takashi Nimura

Diffuse large cell lymphoma occurring in a patient with waldenström's macroglobulinemia. Evidence for the two different clones in richter's syndrome

The authors report a 60‐year‐old man with Richters syndrome, or diffuse large cell lymphoma (DLCL) occurring in a patient with either chronic lymphocytic leukemia (CLL) or Waldenströms macroglobulinemia (WM). Surface marker analysis revealed that the WM showed μK surface immunoglobulin (Ig) chains, and that the DLCL showed μλ Ig chains. Flow cytometric DNA analysis demonstrated DNA content differences between WM and DLCL, the former diploid and the latter aneuploid. The current study suggests that Richters syndrome derives from two independent B‐cell malignancies.

Duplication of chromosome 9 carrying a BCR/ABL chimeric gene in Philadelphia chromosome negative chronic myeloid leukemia

We investigated a patient with Philadelphia chromosome (Ph) negative but BCR positive chronic myeloid leukemia (CML) by fluorescence in situ hybridization (FISH). In the chronic phase one chromosome 9 contained a BCR/ABL fusion gene instead of chromosome 22. Although in blast crisis, both chromosomes 9 had BCR/ABL fusion genes. This could be caused by duplication of the rearranged chromosome 9, which may have a significance similar to a double Ph chromosome. This may suggest that the critical event in CML is the formation of a BCR/ABL chimeric gene regardless of its locus in the genome.

A New Variant Translocation of t(15;17) in a Patient with Acute Promyelocytic Leukemia (M3): t(15;19;17)(q22;p13;q12)

The reciprocal translocation (15;17) is specifically associated with acute promyelocytic leukemia [APL; M3 subtype according to French-American-British (FAB) classification]. A few patients with this disease have complex variant translocations. We describe a patient with M3 carrying t(15;19;17)(q22;p13;q12), which is a new type of variant translocation. The karyotypic interpretation was confirmed by Southern blot analysis with the use of RAR alpha and by fluorescence in situ hybridization (FISH) with the use of painting probes of chromosomes 15, 17, and 19 and a (15;17) translocation DNA probe. The results support the idea that the key event in APL is the formation of fusion gene PML/RAR alpha on the der(15).

Translocation (8;17)(p21;q21), a possible variant of t(15;17), in acute promyelocytic leukemia.

We report a 64-year old man with typical features of acute promyelocytic leukemia (APL) [M3, French-American-British (FAB) classification] in whom a variant, t(8;17)(p21;q21), was detected. This is the second case of the same variant translocation to be reported. The breakpoint on 17q was similar to those described in cases with a standard translocation 15;17. Consequently, this chromosome break or rearrangement at band 17q21, rather than the recipient site of translocation of the deleted material, appears to be of crucial importance in the genesis of APL.

Translocation (8;12;21)(q22.1;q24.1;q22.1): A New Masked Type of t(8;21)(q22;q22) in a Patient with Acute Myeloid Leukemia

The translocation t(8;21)(q22;q22) is found in 40% of cases of acute myeloid leukemia (AML) designated as the subtype M2 in the French-American-British (FAB) classification. The 8;21 translocation is clinically of interest because patients with this subtype have a good prognosis. We describe a masked type of the translocation, t(8;12;21)(q22.1;q24.1;q22.1). The translocation was first interpreted as t(8;12)(q22;q24) based on cytogenetics, but was reevaluated as a result of Southern blot and fluorescence in situ hybridization (FISH) analyses.

11q23 Aberration is an additional chromosomal change in de novo acute leukemia after treatment with etoposide and mitoxantrone

We report on 2 patients with acute leukemia who had an 11q23 chromosomal aberration as an additional change after treatment with etoposide and mitoxantrone, agents that affect topoisomerase II (Topo II). One patient with Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (L2) received chemotherapy, including 1,000 mg of etoposide and 75 mg of mitoxantrone. She relapsed 10 months later. Analysis at time of relapse showed a chromosomal aberration of del(11)(q23) as an additional cytogenetic change. The other patient was diagnosed with acute monoblastic leukemia (M5a) and received two autologous peripheral blood stem‐cell transplantations. Her cumulative doses of etoposide and mitoxantrone were 6,000 mg and 42 mg, respectively. She also relapsed, and analysis at that time revealed del(11)(q23) as an additional chromosomal aberration. The mixed lineage leukemia/(myeloid‐lymphoid leukemia (MLL) gene was not rearranged in either case, making these cases distinct from previously described therapy‐related leukemias caused by Topo II Inhibitors. Based on these two cases, it may be that Topo II inhibitors can cause clonal evolution affecting chromosome band 11q23.

REARRANGEMENTS OF THE BCL6 GENE AND CHROMOSOME ABERRATIONS AFFECTING 3Q27 IN 54 PATIENTS WITH NON-HODGKIN'S LYMPHOMA

Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkins lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was reported. We performed molecular studies of the BCL6 gene in 54 patients with NHL. Twelve patients (22%) with rearranged BCL6 genes were selected for histological, clinical, molecular, and cytogenetic studies. Ten of these cases were diffuse, large cell type lymphoma, one a follicular lymphoma, and one a mantle cell lymphoma (MCL). All cases were of the B-cell type and this is the first time a rearranged BCL6 gene has been found in an MCL. Cytogenetic data for 10 cases were available and the partner sites of the 3q27 translocation were determined in 7 of 10 patients. These locations were variable, including 6p21.3, 9p22, and 14q11 in addition to the immunoglobulin loci 14q32 (IGH), 2p12 (IGK), and 22q11 (IGL). The heterogeneity in partner sites is distinct from other lymphoma subgroups and may suggest that the genetic events are not uniform among patients with BCL6 rearrangements.

Risk Factors for Hepatosplenic Abscesses in Patients With Acute Leukemia Receiving Empiric Azole Treatment

The authors retrospectively evaluated 63 febrile neutropenic episodes in 33 consecutive patients with leukemia who received empiric azole treatment for refractory or relapsing fever that occurred despite broad-spectrum antibiotics. In 8 patients (24%), hepatosplenic abscesses (HSA) developed. To identify the risk factors for the development of HSA, the authors compared various characteristics of febrile episodes in those with and without HSA. The risk factors included relapsed status of leukemia (P = 0.04) and Candida colonization of surveillance cultures from the throat (P = 0.03) and stool (P = 0.03). However, the duration of neutropenia, gastrointestinal symptoms, types of chemotherapy, and leukemia subtypes were not correlated with the development of HSA. Based on these results, the authors identified the high risk group for the development for HSA as patients with relapsed leukemia with fungal colonization of gastrointestinal tract during neutropenia despite empiric antifungal treatment with azoles.

BCL6 rearrangement in a patient with mantle cell lymphoma

Abstract We describe a patient with mantle cell lymphoma (MCL) associated with BCL6 gene rearrangement. MCL is a distinct subtype of non-Hodgkins lymphoma characterized by CD5+, CD10–, CD20+, t(11;14)(q13;q32) and PRAD1/cyclin D1 overexpression. Although rearrangement of the BCL6 gene is the most frequent genetic change among diffuse lymphomas and some follicular lymphomas this is the first report of a patient with MCL associated with BCL6 rearrangement.

Acute Myelogenous Leukemia Associated with a Mediastinal Tumor

We describe a 45-year-old female who developed acute myelogenous leukemia (AML) associated with a mediastinal mass. The patient achieved a complete remission accompanied by resolution of the mediastinal mass following intensive chemotherapy alone. A review of the literature disclosed ten AML patients with a mediastinal tumor; all five patients who had mediastinal granulocytic sarcoma treated by local irradiation prior to developing AML, eventually relapsed as frank leukemia and died soon afterwards. On the other hand, three of the other five patients who simultaneously developed both a mediastinal tumor and overt AML achieved complete remission with combination chemotherapy. In conclusion, intensive chemotherapy should be considered for a patient with granulocytic sarcoma of the mediastinum, irrespective of the concomitant leukemia.