Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor- beta gene rearrangement

A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T- acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32–34;q24),t(9;12) (p22;p12–13). Reciprocal translocations involving chromosome bands 7q32–36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32–36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T- cell phenotype.</jats:p

Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor- beta gene rearrangement

Abstract A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T- acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32–34;q24),t(9;12) (p22;p12–13). Reciprocal translocations involving chromosome bands 7q32–36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32–36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T- cell phenotype.</jats:p

t(1;3)(p36;q21) in acute nonlymphocytic leukemia: a new cytogenetic- clinicopathologic association

A number of specific chromosomal abnormalities have been associated with distinctive clinical and/or morphological subtypes of acute nonlymphocytic leukemia (ANLL) in recent years. We have studied three patients with ANLL and t(1;3)(p36;q21). Each had weakness as their major complaint, a moderately severe anemia and, for ANLL, a relatively high platelet count. All three demonstrated abnormalities of the megakaryocytic, erythroid and granulocytic lineages. Most striking was the dysmegakaryocytopoiesis. The blasts in all three patients showed relatively few azurophilic granules, one to four prominent nucleoli, and rare peroxidase positivity. No patient had Auer rods. No patient responded to standard chemotherapy regimens. The data suggest that t(1;3)(p36;q21) identifies a new cytogenetic-clinicopathologic subtype of ANLL.</jats:p

A collaborative study of the relationship of the morphological type of acute non-lymphocytic leukemia with patients'age and karyotype.

consecutive patients with nonlymphocytic leukemia from six independent laboratories in the United States. Europe. and Australia were combined. The karyotypic pattern determined with banding was correlated with the patient’s age and the morphological type of leukemia according to the FAB classification. Of the 503 patients in the combined study. 260 had acute myeloblastic leukemia (AML. Ml and M2). 142 had acute myelomonocytic leukemia (AMMoL, M4). 43 had acute monocytic leukemia (AMoL. M5). 30 had erythroleukemia (EL. M6). and 28 had acute promyelocytic leukemia (API. M3). The percentage of patients with an abnormal karyotype was higher in EL (63%) and AMI (59%) than in AMMoL (40%) and AMoL (42%). In AML, the chromosome pattern showed a clear correlation with age. The consistent translocation involving nos. 8 and 21 . which is specifically associated with AML M2. occurred with the greatest frequency in younger patients. particularly those under the age of 45 yr. Other abnormalities. notably loss of no. 5 or part of its long arm. were not seen in children and showed a progressive increase in frequency with increasing age. Still other abnormalities. such as - 7 or + 8. were present in all age groups. but were more common in older than in younger groups. In AMMoL. on the other hand. loss of no. 5 was rare. loss of no. 7 was less frequent in older than in younger patients. and gain of no. 8 showed some increase with age. Young patients with AMoL had either a+ 8 or a translocation involving the long arm of no. 11 (1 1 q23); older patients also had +8 or various other changes. with loss of no. 7 rare and loss of no. 5 not observed in any patient. In EL. the percentage of aneuploid patients was highest particularly in older patients. of whom 75% had an abnormal karyotype. Although loss of no. 5 or no. 7 was not seen in any patient under age 50. loss of one or both was seen in 47% of all EL patients over age 50. On the other hand. a + 8 was almost twice as common in younger than in older patients. In APL. 39% had the t(1 5;1 7) that is specifically associated with this type of leukemia; other abnormalities were seen in a few older patients. In summary. loss of no. 5 and/or no. 7 occurred in 30% of all EL patients. in 1 9% of all AMI patients. and in only 7% of AMMoL. in 5% of AMoL. and in 4% of APL patients. These observations are significant because patients with ANIL secondary to aggressive therapy for a primary malignant disease tend to have AML or EL. and the majority have - 5 and/or - 7. These same morphological types of leukemia and the same abnormalities. - 5 and I or - 7. are also increased in patients with ANLL de novo who have a history of occupational exposure to potentially mutagenic substances. In the future. the type of leukemia and the particular karyotypic pattern may be useful in identifying a subset of patients with ANLL de novo whose leukemia may be mutagen-induced