Akitaka Suzuki

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

Summary. We encountered a patient with Philadelphia‐negative chronic myeloid leukaemia, witht(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.

Quantification of human herpesvirus 6 in healthy volunteers and patients with lymphoproliferative disorders by PCR-ELISA

To determine whether actual numbers of human herpesvirus 6 (HHV-6) genome in hematologic neoplasias are associated with disease condition, we developed a quantitative PCR-ELISA for detection of HHV-6. The amount of viral DNA was determined using externally amplified known amounts of the plasmid DNA containing the viral target sequences. First, we determined a viral burden in peripheral blood leukocytes obtained from 23 healthy volunteers and four specimens of lymph nodes with reactive hyperplasia. Using 1 microg of DNA, the prevalence of HHV-6 was 43.4% (10/23), ranging from 0 to 100 HHV-6 genomes in blood obtained from healthy volunteers. The amounts of HHV-6 genomes were < 10 in four non-neoplastic lymph node specimens. We next examined the amount of viral DNA in 21 blood specimens and 19 lymph node specimens obtained from patients with lymphoproliferative diseases (LPD) at the time of diagnosis. The number of HHV-6 genomes in most of the B-cell lymphoma was < 5 in both blood and lymph node specimens, however, two lymph node specimens obtained from immunoblastic lymphadenopathy (IBL) and T-cell lymphoma had very high levels of HHV-6 viral DNA (3705 and 810, respectively). We also found that HHV-6 genomes in peripheral blood were more than 1000 in two patients with chronic lymphocytic leukemia. For all LPD patients combined, there were significantly higher levels of viral DNA (200.6 +/- 654.8 HHV-6 genomes per 1 microg purified DNA) compared to those in healthy volunteers (10.0 +/- 21.0 HHV-6 genomes per 1 microg purified DNA) (P < 0.05). This study demonstrates that a high level of HHV-6 viral DNA is occasionally associated with LPD patients. Although it is still uncertain whether HHV-6 is related to the pathogenesis in LPD or not, our results suggest that measurement of HHV-6 genomes using PCR-ELISA may be useful not only to understand the mechanism of HHV-6 infection in hemopoietic neoplasia but also to manage the care of immnocompromised patients such as bone marrow transplant patients.

Trisomy 10 in Acute Myeloid Leukemia: Three Additional Cases from the Database of the Japan Adult Leukemia Study Group (JALSG) AML-92 and AML-95

To clarify the clinical and hematologic features of a rare numerical chromosome abnormality, we searched for trisomy 10 in acute myelogenous leukemias (AMLs) using the database of the Japan Adult Leukemia Study Group (JALSG) AML 92 and 95. Among the sequentially registered patients of JALSG-AML 92 (655 patients) and JALSG-AML 95 (531 patients), chromosome results were obtained in 1,074 patients (90.6%), and we found 3 patients with trisomy 10 as a sole abnormality. The first patient had an AML-M1 morphology with CD7 antigen; the patient obtained complete remission (CR) with the first course of chemotherapy. The second patient had an AML-M1 morphology without expressing CD7 antigen; this patient obtained CR, but relapsed 3 months later, and underwent allogeneic bone marrow transplantation. He suffered from chronic graft-versus-host disease and expired 38 months after the AML diagnosis. The third patient had AML-M0 with CD7 positivity. He obtained CR; however, brain abscess and cerebral hemorrhage occurred. In the literature, the mean age of patients with trisomy 10 AML is 57.8 years, the gender ratio is M/F = 1.5, and the frequency of M0/M1/M2 is 85.7%. A high incidence (81. 8%) of CD7 expression of leukemia cells is notable. About 73% of patients survived for greater than 12 months.

Thrombocytopenia induced by imatinib mesylate (Glivec) in patients with chronic myelogenous leukemia: is 400 mg daily of imatinib mesylate an optimal starting dose for Japanese patients?

Imatinib mesylate (Glivec) is a potent and selective inhibitor of the tyrosine kinase activity of BCR-ABL. Because the mechanism of action of imatinib mesylate is inhibition of BCR-ABL tyrosine kinase, it seems likely that to achieve maximum therapeutic benefit for chronic myelogenous leukemia (CML), imatinib mesylate must be administered at a dose that maximally inhibits BCR-ABL kinase activity or, alternatively, that inhibits sufficient BCR-ABL kinase activity to induce apoptosis. According to in vitro study results, 1 M levels of imatinib mesylate are optimal for inducing cell death, and 1 M trough levels are achieved in patients using imatinib mesylate at a daily dose of more than 300 mg [1]. In a phase I/II study in which the dose-response curve in chronic-phase CML patients was examined, the therapeutic effect was reported to plateau at a dose at or slightly above 300 mg. In addition, there was no convincing evidence of dose-limiting toxicity in patients receiving a maximum dose of 1000 mg [2]. These data were used to set the standard therapeutic dose of imatinib mesylate for chronicphase patients at 400 mg daily, and thereafter, the therapeutic benefits for CML patients of imatinib mesylate at this dose were demonstrated in clinical trials [2,3]. This standard therapeutic dose has been used in administering imatinib mesylate to Japanese patients as well as patients in the United States and Europe. At our institute, however, a series of CML patients treated with 400 mg of imatinib mesylate showed thrombocytopenia, and imatinib mesylate adminisThrombocytopenia Induced by Imatinib Mesylate (Glivec) in Patients with Chronic Myelogenous Leukemia: Is 400 mg Daily of Imatinib Mesylate an Optimal Starting Dose for Japanese Patients?

Change in a complex translocation involving band 7q34 and 9p‐ in a case of t‐cell lymphoblastic lymphoma

The authors report a case of T‐cell type non‐Hodgkins lymphoma (NHL) in which neoplastic cells possessed a three‐way translocation involving chromosomal bands 3q21 7q34, and 22q11, as well as partial monosomy of the short arm of chromosome 9. In the literature, most reported cases of 7q32|q36 abnormalities had T‐cell type leukemia/lymphoma and were younger than 20 years. Two NHL cases, including the current case, were diagnosed as having lymphoblastic lymphoma with a leukemic transformation. The neoplastic cells of the reported cases commonly showed CD2 (E‐rosette receptors) and CD38. All 17 patients but three manifested a mediastinal mass at diagnosis and seven had central nervous system lesions or pleural infiltration. Furthermore, five of the 19 reported cases also showed 9p‐ change.