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.     

11例伴t(6;11)(q27;q23)急性白血病的临床和实验研究

目的　分析伴有t(6 ;11) (q2 7;q2 3)急性白血病 (AL)的形态学、免疫学、细胞遗传学和临床特点。方法　采用骨髓细胞直接法或短期培养法制备染色体 ,用R显带技术进行核型分析 ;采用双色混合谱系白血病 (MLL)基因探针和间期荧光原位杂交 (FISH)技术 ,对其中 10例AL进行MLL重排检测 ;分别用异硫氰酸荧光素 (FITC)和得克萨斯红 (Texasred)标记的 6号和 11号全染色体涂抹探针对其中 5例标本进行染色体研究。结果　t(6 ;11)易位病例主要见于急性髓系白血病(AML) M5(8/ 11例 )。 11例t(6 ;11)AL中 9例初诊时WBC计数 (10～ 10 0 )× 10 9/L之间 ,9例有不同程度的肝、脾、淋巴结浸润。 9例为单纯t(6 ;11) ,2例伴有其他异常。进行免疫表型分析的 9例白血病中 4例髓系和淋系抗原共表达 ,除 1例外 ,其余患者均有CD3 4 表达。本组t(6 ;11)患者中位生存期为 6个月。 10例患者的双色FISH研究显示均有MLL重排 ,其中 5例标本的涂抹分析也证实 6号和 11号染色体之间发生了相互易位。结论　t(6 ;11)AL有着独特的临床特点 ,其预后不良。染色体涂抹和间期双色FISH技术是检测该易位和MLL重排的可靠手段。     

Novel constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) in patients with acute leukemia

Certain constitutional translocations have been described to be associated with an increased risk of malignant diseases. We report here two patients, one with acute myeloid leukemia (AML) and another with biphenotypic acute leukemia, in whom constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) were observed, respectively. To our knowledge, none of the above translocations has been previously reported.     

Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations

The translocation t(4;11)(q21;q23) is one of the most common specific chromosomal aberrations in acute lymphoblastic leukemia (ALL), occurring in 2% of childhood and in 5–6% of adult cases. Especially in adults, the t(4;11) is associated with a poor prognosis. In order to determine the significance of clonal chromosome aberrations that occur in addition to t(4;11), we studied the karyotypes and clinical courses of 23 patients with acute lymphoblastic leukemia and a translocation t(4;11)(q21;q23). Additional clonal chromosome aberrations were found in ten patients. An isochromosome i(7)(q10) and a trisomy 6 were observed most frequently as secondary anomalies. Clonal evolution was detected in four of six patients analyzed at diagnosis as well as at relapse. With treatment carried out according to modern risk-adapted therapy protocols, no difference in outcome was observed between patients with clonal chromosome aberrations in addition to t(4;11) at diagnosis and those without.     

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.     

Molecular cloning of the breakpoint of t(11;22)(q23;q11) chromosome translocation in an adult acute myelomonocytic leukaemia

Southern blot analysis with a cDNA probe of MLL indicated that the breakpoint is in a Bam HI 8.3 kb fragment which carries the exon 5–11 of MLL gene in DNA from an adult acute myelomonocytic leukaemia with a t(11;22)(q23;q11) translocation. The structural analysis of the rearranged MLL locus demonstrated that the breakpoint is localized between exon 8 and 9 of MLL locus. The normal counterpart fused to the MLL locus was proved to be derived from chromosome 22q11( AF-22 ) by somatic cell hybrids analysis and FISH. By FISH, AF-22 locus was localized to the region more centromeric to the BCR gene.     

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.     

Breakpoint clustering in t(4;11)(q21;q23) acute leukemia.

Chromosome 11 band q23 is commonly involved in nonrandom chromosomal translocations in hematopoietic malignancies, especially in infant acute leukemias. By using pulsed-field gel electrophoresis (PFGE) with restriction endonuclease digests of DNA from both a leukemia cell line (RS4;11) bearing the t(4;11)(q21;q23) and from human/hamster hybrid cells, we have been able to construct a detailed restriction map of the chromosome 11q23 region and have localized the t(4;11) chromosome 11 breakpoint to a region located approximately 200 to 230 kb telomeric to the CD3 gamma region and approximately 580 kb centromeric to the PBGD gene. PFGE analyses of DNA from clinical leukemia specimens and cell lines indicated a tight clustering of breakpoints in all eight t(4;11) acute leukemias studied. These data strongly suggest that discrete genetic loci are interrupted on both chromosomes 4 and 11 in a manner likely to be critically involved in the pathogenesis of t(4;11) acute leukemias. To our knowledge, these results represent the first evidence of breakpoint clustering in t(4;11) acute leukemias. In contrast to t(4;11), other 11q23 abnormalities studied to date have frequently shown evidence for alternative breakpoint sites in 11q23.     

Therapy-Related Acute Myeloid Leukemia 6 Years after Clonal Detection of inv(11)(q21q23) and MLL Gene Rearrangement

Results of recent studies with animal models suggest that expression of MLL fusion proteins promotes acute leukemogenesis. However, the most potent MLL fusion proteins are not sufficient for the development of acute myeloid leukemia (AML). The clinical data on the pathogenesis of this type of leukemia are limited. We analyzed the case of a patient with therapy-related AML with MLL rearrangement. The patient initially developed AML with t(8;21). Although the patient achieved complete remission with chemotherapy, an abnormal karyotype, inv(11)(q21q23), was detected. After 6-year persistence of a clone with the inversion 11 karyotype in the bone marrow, secondary AML developed. Results of fluorescence in situ hybridization analysis combined with magnet-activated cell sorting analysis showed that MLL rearrangement was detected in CD34+ and CD13+ fractions but not in a CD3+ fraction of the bone marrow. There were 2 important clinical findings. One was that MLL rearrangement was not sufficient for the development of leukemia. The other was that MLL rearrangement targets specific lineages.