Philadelphia chromosome in human multiple myeloma.

Four patients with multiple myeloma in whom a Ph1 chromosome was found were described; 1 patient had a (9;22) translocation, 2 had no evidence of a translocation, and 1 had a complex translocation (3;8;22). Ph1 chromosomes with standard (9;22) or with unusual translocations were recently found in various myeloproliferative disorders (other than chronic myelogenous leukemia) and in acute lymphoblastic leukemia. These findings point to the genesis of a Ph1 chromosome in diseases other than chronic myelogenous leukemia and other myeloproliferative disorders.

Translocation (11;15)(q23;q14) in three patients with acute non-lymphoblastic leukemia (ANLL): clinical, cytogenetic and molecular studies.

We report on three patients with acute non-lymphoblastic leukemia (ANLL) displaying the same chromosomal translocation t(11;15)(q23;q14). The clinical course of the disease was aggressive, and survival was short. The FAB subtype was M-2 in two cases, and M-1 in the remaining patient. Immunologically two cases showed aberrant expression of a lymphoid antigen (CD19 and TdT, respectively). HTRX1/MLL gene was rearranged in one patient studied at the time of diagnosis. These results plus data scattered in the literature show that the t(11;15)(q23;q14) can be added to the list of recurrent rearrangements in ANLL involving 11q23.

Small B cell NHL and their leukemic counterpart: differences in subtyping and assessment of leukemic spread.

Three subtypes of small lymphocytic lymphoma were studied, namely B cell chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma (MCL) and follicle center lymphoma (FCL). Agreement between tissue diagnosis, based on the proposal for a revised European-American classification of lymphoid neoplasms from the International Lymphoma Study Group, and the cytomorphological diagnosis on peripheral blood and/or bone marrow smears, using the proposals for the classification of chronic (mature) B and T lymphoid leukemias of the French-American-British Cooperative Group, was studied. Full agreement was found in 90% of the CLL and 82% of the FCL cases. In MCL cases, agreement was 65% including all cases classified as intermediate/mantle zone lymphoma according to FAB criteria. The incidence of bone marrow involvement detection in trephines compared to smears was equal in CLL (both 100%) and slightly higher in MCL (56 vs 48.5%); in FCL, however, trephine biopsies provided more reliable material (71 vs 35%).

11q23 involvement in a complex insertion (10; 11) in acute monocytic leukemia.

A variant insertion (10p; 11q) preceded by a paracentric inversion of the long arm of chromosome 11, inv(11)(q12q23), has been found in a patient with ANLL-M5a. The association of 11q abnormalities involving the breakpoint 11q23 with acute monocytic leukemia is confirmed.

Adult T-cell leukemia: a report on two white patients.

Two white European males are reported with adult T-cell leukemia (ATL), a disease first described in Japan, but recently also in the U.K. and U.S.A. Both patients presented with lymphadenopathy, but without a mediastinal mass. In addition, one patient had skin infiltrates and the other had hepatosplenomegaly. Morphologic and ultrastructural examination of the blasts in bone marrow and lymph node biopsy revealed a predominance of polymorphic lymphoid cells with pronounced nuclear irregularities and a semi-mature chromatine pattern. Histopathology of the lymph nodes showed a diffuse infiltration with medium-sized lymphoblasts with irregular nuclei. The blasts in the bone marrow formed E rosettes with sheep erythrocytes, lacked terminal deoxynucleotidyl transferase (Tdt) activity but expressed the Ia-like antigen; although the majority of the cells reacted with a polyclonal anti-T-cell serum, they were negative for OKT3. In one patient a helper/inducer phenotype (OKT4+) was found in the lymphoblasts of bone marrow and lymph node, while in the other only in the lymph node. The difference between bone marrow and lymph node phenotype is discussed. To our knowledge, these are the first two European patients reported with ATL, a disease clearly different from convoluted T-cell acute lymphocytic leukemia.

Improvement of severe secondary hyperparathyroidism in dialysis patients by intravenous 1 alpha(OH) vitamin D3, oral CaCO3 and low dialysate calcium.

Seventeen patients (9 men, 8 women; aged 27 to 75 years) who were on chronic hemodialysis for 1 to 14 years were included in the study because they had severe hyperparathyroidism diagnosed by elevated plasma alkaline phosphatase and on plasma intact PTH levels more than twice the upper limit of normal. They had been previously treated with various combinations of oral calcium and/or Al(OH)3 as phosphate binders, oral 1 alpha(OH) vitamin D3 metabolites and a dialysate calcium concentration (DCa) of 1.6 to 1.75 mmol/liter. When i.v. alpha calcidol was introduced DCa was reduced to 1.25 mmol/liter and CaCO3 taken with the meal was used as the sole phosphate binder. alpha calcidol was i.v. injected after the third dialysis of the week at a dose up to 4 micrograms per dialysis in order to obtain a predialysis plasma concentration of Ca at 2.5 +/- 0.2 and PO4 between 1.5 and 2 mmol/liter. All the other treatments were discontinued. During the six months of follow-up, the mean weekly dose of alpha calcidol was 6 micrograms and CaCO3 700 +/- 50 mmol. Plasma calcium (PCa) increased moderately from 2.35 to 2.47 mmol/liter (P < 0.05) whereas plasma PO4 (PPO4) did not significantly increase (1.56/1.64 mmol/liter). Total alkaline phosphatase and its bone isoenzyme activity decreased significantly to normal values [respectively from 186 to 83 IU (normal: 135) and from 102 to 32 IU (normal < 33)] whereas plasma intact PTH decreased from 485 to 125 pg/ml (normal < 55).(ABSTRACT TRUNCATED AT 250 WORDS)

Inversion (4)(p13q28) in two cases of acute nonlymphocytic leukemia.

An identical inversion, inv(4)(p13q28), was found to occur as the sole karyotypic anomaly in two patients with acute nonlymphocytic leukemia. The breakpoints are different from any previously described structural rearrangements of chromosome 4.

The karyotype in secondary hematologic disorders after treatment for Hodgkin's disease. A study of 19 patients.

In 19 cases of secondary hematologic disorders in patients previously treated for Hodgkin's disease, chromosome aberrations were analyzed in relation to the type of previous chemo- and/or radiotherapy, age of the patients, histopathologic features of the Hodgkin's disease at diagnosis, time interval between the treatment and the occurrence of the secondary disorder, and survival. The karyotype was of significant prognostic value when three cytogenetic groups were considered: patients with normal karyotypes; patients with aberrations of chromosome 7 as the sole anomaly; and patients with complex rearrangements and translocations. The last group showed the lowest rate of survival. Bone marrow transplantation was successful in two patients with a normal karyotype.

Translocation t(1;3)(p36;q21) in malignant myeloid stem cell disorders.

A t(1;3)(p36;q21) translocation was found in bone marrow samples of two patients with hematologic disorders. One patient had a myelodysplastic syndrome evolving into acute nonlymphocytic leukemia (ANLL) M1 and the second patient had ANLL-M6 secondary to treatment for Hodgkin's disease. Because myelodysplastic syndromes and secondary leukemia are stem cell disorders, the t(1;3)(p36;q21) appears to be a chromosome abnormality in malignant myeloid stem cells.

Acute nonlymphoblastic leukemia with bone marrow eosinophilia and structural anomaly of chromosome 16.

A patient with acute myelocytic leukemia in relapse presented with t(16;21) (p12;q22). Hematologic studies revealed a large number of abnormal eosinophils in the bone marrow. The complexity of chromosome #16 rearrangements associated with acute nonlymphocytic leukemia and the possible significance of chromosomes #16 and #21 in relation to the concomitant eosinophilia are briefly discussed.

Characterization by chromosome painting of balanced and unbalanced X chromosome translocations in myelodysplastic syndromes.

Structural anomalies of the X chromosome, especially translocations, are rare events in myelodysplastic syndromes (MDS). In a series of 2270 MDS patients analyzed between 1983 and 1994 (Center for Human Genetics, Leuven), 9 cases were found with translocations involving the X chromosome. These aberrations were not restricted to specific FAB subtypes and were the sole anomalies in 3 cases. In the remaining 6 patients, they were associated with other abnormalities, including 5q-, observed in three cases. Fluorescence in situ hybridization (FISH) was retrospectively performed on 8 patients and was shown to be a useful complement for the characterization of the translocations involving the X chromosome. In 3 cases, we could identify translocation partners and breakpoint regions only by using chromosome painting. No recurrent chromosome partners were observed. The breakpoints could be localized along the whole X chromosome. There was, however, a cluster in the Xq13 region involved in 4 of the 9 patients. The previously reported association of Xq13 anomalies with refractory anemia with ringed sideroblasts (RARS) was found in only one case. Despite the lack of characteristic translocations involving the X chromosome, the occurrence of such changes as the sole karyotypic anomaly suggests that they could play a role in the pathogenesis of some myelodysplastic syndromes.

Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome.

Clinical, cytomorphologic, and cytogenetic investigations were carried out in a series of 76 secondary MDS and ANLL. Chromosome abnormalities were more frequent in patients with a history of multiple myeloma or macroglobulinemia (92%) and myeloproliferative disorders (82%) than in patients with previous breast cancer (40%). The secondary hematologic malignancies were mostly a trilineage bone marrow disorder. The most commonly found cytogenetic anomaly was monosomy 7, followed by total or partial loss of chromosome 5. In addition six other chromosomes, i.e., chromosome 3, 8, 9, 12, 17, and 21 seemed to be consistently involved in the pathogenetic mechanisms of secondary leukemia and MDS.

11q-chromosome is associated with abnormal iron stores in myelodysplastic syndromes.

Nine cases of myelodysplastic syndrome with a deletion of the long arm of chromosome #11 (11q-) showed ringed sideroblasts, and three of which had an acquired sideroblastic anemia according to the criteria of the FAB classification. In contrast, among four cases of myelodysplastic syndromes with translocation of extra material to the long arm of chromosome #11 (11q+), only one showed bone marrow sideroblasts. These results strongly indicate that an 11q- chromosome is a marker of iron overload in myelodysplastic syndromes. Within the cases of 11q- associated with sideroblastosis, two cytogenetically different anomalies (i.e., terminal or interstitial deletions) were delineated.

Therapy-related acute myeloid leukemia with t(8;16)(p11;p13) following anthracycline-based therapy for nonmetastatic osteosarcoma.

A case of therapy-related AML with t(8;16)(p11;p13) 14 months following the end of anthracycline-containing chemotherapy for a nonmetastatic osteosarcoma of the left tibia is presented. The patient was successfully treated with intensive remission-induction chemotherapy. Subsequently, he underwent an uncomplicated allogeneic bone marrow transplantation from his HLA-identical brother and is at present alive and disease-free 10 months after diagnosis of the secondary AML.

Pentasomy 21 characterizing spontaneously regressing congenital acute leukemia.

Pentasomy 21 was found to characterize the proliferating cells in a case of transient congenital acute leukemia (or congenital acute leukemia) with spontaneous remission. The patient was phenotypically normal, and cytogenetically no evidence could be found for the existence of a mosaic with a normal cell line and one with more than two No 21 chromosomes. The importance of these findings is discussed.

5q- anomaly in a patient with disseminated teratoma.

A 5q- anomaly associated with other chromosome anomalies was found in the infiltrated bone marrow of a patient with a highly malignant teratoma originally located in the mediastinum. There was no evidence of a second malignancy, and it is likely that the 5q- anomaly was, indeed, associated with the malignant teratoma cells.

Translocation t(3;17)(q26;q22): a marker of acute disease in myeloproliferative disorders?

A new reciprocal translocation, t(3;17)(q26;q22), has been observed in three patients with myeloproliferative disease. The t(3;17) seems to be associated with acceleration of the disorder, thus adding further evidence to a relationship between 17q22 rearrangements and acute myeloproliferation .

Translocation (Y;1)(q12;q12) in hematologic malignancies. Report on two new cases, FISH characterization, and review of the literature.

Translocation (Y;1)(q12;q12) is a rare cytogenetic anomaly occurring in hematologic disorders thought to affect stem cells. We report here on two new cases, one end-stage myelofibrosis and one chronic myelomonocytic leukemia. The translocation breakpoints were assessed by conventional cytogenetic techniques in both cases and by FISH in the second case. A partial trisomy of the 1q21-qter region could be demonstrated. The data of the literature are reviewed and the possible pathogenetic mechanisms are discussed.

Translocation t(6;9) occurring in acute myelofibrosis, myelodysplastic syndrome, and acute nonlymphocytic leukemia suggests multipotent stem cell involvement.

The cytological and cytogenetic features of six patients with myeloid neoplasia and t(6;9)(p23;q34) including a case of acute myelofibrosis (AMF), a refractory anemia with excess of blasts (RAEB), and four cases of acute nonlymphocytic leukemia (ANLL) are described. Two patients in this series, both affected by ANLL type M2, presented an increase of bone marrow basophils, suggesting that this cytological-cytogenetic association is not absolute and that it may be more frequently observed in ANLL with maturation. All patients with de novo ANLL showed associated myelodysplastic features, and one patient presented a dysmyelopoietic syndrome, later evolving into ANLL. The presence of the t(6;9) in a range of myeloid neoplasias, with either concurrent myelodysplastic features or a preleukemic phase in cases of ANLL, provide evidence that this chromosome aberration may always involve a multipotent myeloid stem cell. Data on toxic exposure of the patients suggests that myeloproliferative disorders with the t(6;9) may frequently represent environmentally induced neoplasias.

del(7q) in chronic B-cell lymphoid malignancies.

Twelve patients with diagnosis of B-cell non-Hodgkin's lymphoma/leukemia and del[7q] were studied for their clinical, cytogenetic, and molecular characteristics. Eleven patients were classified as small cell lymphoma whereas one had a diffuse large cell lymphoma. Lymphoplasmacytic features were observed in six out of eleven small cell lymphomas. Morphologically and immunologically these small cell lymphomas could be classified as chronic lymphocytic leukemia (typical or atypical; 4 cases), marginal zone lymphoma (splenic lymphoma with villous lymphocytes; 1 case), mantle cell lymphoma (2 cases), or nonspecified, non-Hodgkin's lymphoma (4 cases). Eleven of twelve patients presented with peripheral blood and bone marrow involvement. Two of twelve cases showed del[7q] as the sole anomaly. Two different types of deletions were present: ten cases had del(7)(q21q31) and two cases had del(7)(q31q34). Cases that could be molecularly investigated did not show any involvement of BCL2, BCL3, or BCL6, and only one case had BCL1 rearrangement. The data indicate that del(7q) is associated with a subset of mature small B-cell lymphoproliferative disorders of which some but not all show lymphoplasmatic features.