Double-hit lymphoma with t(8;14)(q24;q32) and t(12;14)(q24;q32) chromosomal translocations

A 50-year-old man presented with an ileocecal tumor and a large amount of ascites. Lymphoma cells obtained from the ascitic fluid were CD10(+), CD20(+), CD38(+), HLA-DR(+), BCL6(-), MUM1/IRF4(+), BCL2(+), and immunoglobulin μ/γ(+). The karyotype determined by G-banding and spectral karyotyping was 46, XY, der(3)t(1;3)(q12;p12), -4, +7, t(8;14)(q24;q32), t(12;14)(q24;q32), der(17)t(4;17)(q21;p11). Fluorescence in situ hybridization disclosed that 93% of interphase cells were positive for the c-MYC and immunoglobulin heavy chain gene fusion. The patient was treated with intensive chemo-immunotherapy, resulting in a complete response. The t(8;14)-t(12;14) double-hit may have generated molecular abnormalities analogous to those of a previously cloned three-way translocation t(8;12;14).     

Translocations t(X;14)(q28;q11) and t(Y;14)(q12;q11) in T-cell prolymphocytic leukemia

We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derived from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8+. The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed.     

Acute lymphoblastic leukemia (L3) with t(2;3)(p12;q27), t(14;18)(q32;q21), and t(8;22)(q24;q11)

A 50-year-old woman developed a subcutaneous tumor in the left lower leg. A biopsy led to the diagnosis of lymphoid malignancy. The malignant cells showed a B-cell immunophenotype. Karyotyping of the cells revealed t(14;18) and t(2;3). The patient was treated with chemotherapy, resulting in a transient response. Subsequently, tumor regrowth and bone marrow recurrence developed. Karyotyping of the bone marrow at relapse revealed a t(8;22) in addition to t(14;18) and t(2;3), which led to a diagnosis of acute lymphoblastic leukemia (ALL)-L3 (FAB). Although the patient was treated with several chemotherapy regimens, the disease was refractory to all the treatments. Fluorescence in situ hybridization (FISH) and the nested polymerase chain reaction (PCR) technique demonstrated rearrangements of the c-myc, bcl-2, and bcl-6 genes. ALL-L3 associated with t(14;18) is known to be complicated frequently with cerebrospinal infiltration and extramedullary lesions, and has a poor prognosis. In our case, the presence of the additional t(2;3) may have enhanced this patient's refractoriness to the treatment.     

Therapy-related acute promyelocytic leukemia with a t(9;22)(q34;q11) and t(15;17)(q22;q11 to approximately 12) subclone

The translocation (15;17) is a typical marker of acute promyelocytic leukemia, whereas t(9;22) is predominantly associated with chronic myelogenous leukemia, and seldom with acute myelogenous leukemia. Furthermore, the association between t(15;17) and t(9;22) in the same cell is extremely rare. We present a case of therapy-related acute promyelocytic leukemia (t-APL) with a subclone accompanied by karyotype 46, XX, t(9; 22)(q34;q11), t(15 ;17)(q22;11 to approximately 12) at onset. A 75-year-old woman was diagnosed as having non-Hodgkin lymphoma of the thyroid gland in July 1997. She was treated with a CHOP-like regimen, but complete remission (CR) was not achieved. She then underwent surgical resection of her thyroid gland, and was treated with etoposide (total dose 16775 mg) from February 1998 to May 2000. In June 2000, having developed t-APL, she was referred to our department. The patient attained CR following treatment with chemotherapy containing all-trans retinoic acid. Ten months later she relapsed, but lost the t(9;22), while maintaining the t(15;17).     

A subtype of the prototypic karyotype in acute myeloid leukemia t (8; 21) (q22; q22), del 9 (q13; q23)

Summary Two patients with acute myeloid leukemia are described in whom G- and C-banding analysis of bone marrow cells revealed, besides the translocation t(8;21), an additional structural anomaly characterized by the deletion of bands q13 to q23 of one chromosome no. 9. Findings in the literature support the proposal that this constellation represents a hitherto unreported subtype of the prototypic karyotype in AML.Supported by the Deutsche Forschungsgemeinschaft (SFB 102)     

Acute promyelocytic leukemia with t(11;17)(q23;q21)

We report the first Japanese case of acute promyelocytic leukemia with t(11;17)(q23;q21) and CD56. A 41-year-old man with schizophrenia was hospitalized because of the appearance of blasts with Auer bodies in his peripheral blood. A bone marrow smear showed an abundance of abnormal cells with scanty azurophile granules in the cytoplasm and somewhat lobulated nuclei. Because the abnormal cells demonstrated strongly positive peroxidase reactivity with a few faggot bodies, the patient was given a diagnosis of acute promyelocytic leukemia (M3v according to the FAB classification). However, chromosome analysis revealed t(11;17)(23; q21). All-trans retinoic acid (ATRA) was not effective. Mitoxantrone was more effective than daunorubicin, and resulted in a complete remission with a normal karyotype. About 9 months later, the patient suffered a relapse. Surface marker analysis demonstrated blasts that were positive for CD56, CD13, and CD33. MEC (mitoxantrone, etoposide, cytarabine) therapy was ineffective. Although ATRA was administered at a dose of 80 mg/day for more than 2 months, the number of myelocytes and promyelocytes increased Finally CAG (cytarabine, aclarubicin, G-CSF) therapy was initiated, but the patient died due to intracranial invasion and hemorrhage accompanied by disseminated intravascular coagulation.     

Translocation (1;5)(q23;q33) in adult acute non-lymphocytic leukemia

Chromosome banding studies carried out on bone marrow cells from a 57-year-old white caucasian male with an M1 acute non-lymphocytic leukemia (ANLL) revealed an unbalanced translocation involving chromosomes 1 and 5 [der(5)t(1;5)(q23;q33)] as part of complex abnormalities in 76% of the cells analyzed. This chromosomal abnormality is the first to be reported in an adult patient with acute non-lymphocytic leukemia. A review of previous reports on translocations involving the juxtaposition of the 1q23----qter DNA segment to other chromosomes suggests that this new translocation may be specifically involved with abnormal myeloid proliferation.     

Diffuse large B-cell lymphoma carrying both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32)

We report a 60-year-old man with diffuse large B-cell lymphoma harboring both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32). Although he received six courses of conventional combination chemotherapy plus rituximab, early relapse occurred. Four courses of an intensive salvage regimen and high-dose chemotherapy with autologous peripheral blood stem cell transplantation were performed. The patient has remained in complete remission for over 24 months. This case is noteworthy because both genetic abnormalities are implicated in lymphomagenesis.