Mature B-cell acute lymphoblastic leukemia with t(9;11) translocation: a distinct subset of B-cell acute lymphoblastic leukemia.

Mature B-cell acute lymphoblastic leukemia (ALL) is typically associated with the FAB-L3 morphology and rearrangement of the MYC gene, features characteristic of the leukemic phase of Burkitt's lymphoma. However, the term 'mature' has also been used to describe other rare cases of B-ALL with light-chain surface immunoglobulin expression. In contrast, infantile B-cell ALL is generally characterized by rearrangement of the MLL gene, an immature pro-B-cell phenotype, and CD10 negativity. We describe two unusual cases of infantile B-ALL with non-L3 morphology, expressing a mature B-cell phenotype (lambda sIg+, CD19+, CD10-, TdT-, and CD34-), and showing MLL rearrangement without MYC rearrangement at presentation. Both infants relapsed after months of morphologic and genetic remission. At relapse, the t(9;11) translocation was detected in both cases by spectral karyotyping. After the initial relapse, both cases followed a rapid and aggressive course. Literature search identified few similar cases, all expressed lambda surface immunoglobulin and showed MLL rearrangement (majority with the t(9;11) translocation). These cases show that B-ALL with MLL rearrangement, especially the t(9;11) translocation, can express a 'mature' B-cell phenotype and may represent a distinct subset. Identification of additional cases will further clarify the significance of MLL rearrangements in mature B-ALL.     

A translocation t(9;11)(p11;q23) in T-cell acute lymphoblastic leukemia (FAB-l2)

We here report a t(9;11)(p11;q23) as the only abnormality in the affected cells of a 20-year-old male with acute lymphoblastic leukemia (L2) of T-cell origin. One hundred six patients with acute leukemia and involvement of band 11q23 were reviewed. Young age, hyperleukocytosis, and poor prognosis characterized almost all the cases in the acute leukemias with the 11q23 translocation, despite involvement of different recipient chromosomes and different morphologic and immunologic phenotypes.     

Immunoglobulin gene rearrangements in acute lymphoblastic leukemia with the 9;11 translocation

The recurring chromosomal 9;11 translocation [t(9;11) (p22;q23)] typically is associated with acute monoblastic leukemia, but a number of patients with acute lymphoblastic leukemia also have been reported to have the t(9;11). To investigate the cell lineage in the latter cases, we analyzed DNA from the leukemic cells of an 8-year-old girl with acute lymphoblastic leukemia and a t(9;11) for rearrangements of the immunoglobulin and T-cell receptor genes. Rearrangements of both immunoglobulin heavy-chain loci and of one lambda light-chain gene were detected, as well as deletions affecting both alleles of the kappa light-chain genes; T-cell receptor genes were in germline configuration. These results provide further evidence that the 9;11 translocation is not limited to myeloid lineage leukemia and may be observed in acute lymphoblastic leukemia.     

t( 12;21): A new recurrent translocation in acute lymphoblastic leukemia

A t(12;21)(p11 -p12;q22) was detected by chromosome painting in three patients with acute lymphoblastic leukemia (ALL) among eight ALL cases with 12p- abnormalities. The three leukemias had similar immunophenotypes (DR+, CD10 +, CD19 + ). Fluorescence in situ hybridization (FISH) experiments using YAC clones from 21q21-q22 were performed to better localize the breakpoint on chromosome 21. This breakpoint was localized to 21q22.2 in one patient. Although only one case of ALL with t( 12;21) has been reported previously, the present results suggest that t( 12;21) is a recurrent translocation in ALL. Genes Chrom Cancer 9:186-191 (1994). © 1994 Wiley-Liss, Inc.     

t(1;19) and t(12;17) in childhood acute lymphoblastic leukemia of pre-B type

We report on a patient with pre-B acute lymphoblastic leukemia (ALL) and t(t;19) as the principal chromosomal abnormality. The presence of the subsequent t(12;17) and the correlation between the chromosomal anomalies and the immunologic phenotype is discussed.     

T-cell acute lymphoblastic leukemia with translocation (1;18)

A case of T-cell acute lymphoblastic leukemia with a translocation between chromosomes #1 and #18 is described. The breakpoints were at bands 1q23 and 18q21. A single cell contained the translocation t(1;19)(q23;p13). The breakpoint on chromosome #1 was the same in both translocations, and the breakpoint on chromosome #18 was the same as that in t(14;18)(q32;q21) associated with follicular lymphoma. The possible relationship between chromosome bands 1q23 and 18q21 and the morphologic features of the leukemia cells is discussed.     

Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts

We asked herein whether functional dendritic-like cells could be generated from t(9;22) acute lymphoblastic leukemia (ALL) blasts. We first determined that the combination of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor-alpha, stem cell factor and CD40 ligand was optimal for generating dendritic-like cells from t(9;22) ALL cell lines. Following 6 days in culture, four of five cell lines demonstrated dendrite-like morphology, upregulation of CCR7, CD54, CD80 and CD86, uptake of extracellular proteins and activation of T cells, and similar results were obtained with blasts from three t(9;22) ALL patients. The dendritic-like cells appeared to be composed of populations resembling both immature and mature dendritic cells (DCs), distinguished by CD80 expression. CD80-CD86+ cells were classified as immature DCs, demonstrating high endocytic capability and inducing minimal allogeneic T cell proliferation, while CD80+CD86+ cells were classified as mature DCs, exhibiting negligible endocytic capability and inducing robust allogeneic T cell proliferation. These mature dendritic-like cells induced autologous cytotoxic T cell responses against the unmodified blasts in a patient who achieved prolonged remission. In summary, CD80+CD86+ cells generated from t(9;22) ALL blasts may be useful in adoptive immunotherapy for t(9;22) ALL.     

4;11 translocation in acute lymphoblastic leukemia: A specific syndrome

Three patients with acute lymphoblastic leukemia (ALL) having t(4;11) (q21;q23) are described. Their clinical characteristics are compared with ten other published cases all involving similar histories and poor prognoses.     

Reciprocal translocation (11;19)(q23;p13) in congenital acute lymphoblastic leukemia

The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.     

Unusual t(3;12)(q28;q13) in childhood acute lymphoblastic leukemia

In this article we report a case of a 7-year-old boy affected by acute lymphoblastic leukemia of the common type. Bone marrow examination at diagnosis showed a reciprocal translocation between the long arm of chromosome 3 and the long arm of chromosome 12. This previously unpublished translocation is discussed and compared to the findings in the current literature.     

Transposition of the oncogene ets-1 in t(11;19) translocation in acute leukemia

The specific chromosomal rearrangement t(11;19)(q23;p13) has been identified as a nonrandom chromosomal rearrangement in acute leukemia. The breakpoint, 11q23, coincides with the ets-1 oncogene locus. However, only very few studies have been done to verify the genomic alteration and transposition of ets-1 in the t(11;19) chromosomal rearrangement. In the present study, we identified the t(11;19)(q23;p13) translocation in two acute leukemic cases. One of the cases, biphenotypic leukemia, has been followed thoroughly. An abnormal karyotype was identified in the patient's blood and marrow samples at diagnosis and at relapse, while only normal karyotypes were identified at remission.

In situ hybridization of chromosomal preparations with the ets-1 probe pHE5.4 resulted in silver grains nonrandomly localized to 19p13 in the metaphase spreads prepared from the blood sample taken at relapse, while no detectable grains were found on chromosome 19p13 in a sample taken at remission. To determine if genomic alterations of ets-1 are associated with this translocation, Southern blot hybridizations with the pHE5.4 probe were performed on deoxyribonucleic acid (DNA) isolated from blood or marrow samples of the patient at remission and relapse as well as on DNA from a disease-free normal control. Any DNA digested with AvalI, SstI, XbaI, and Bam HI, followed by hybridization with pHE5.4, demonstrated no genomic alterations or amplification of the ets-1 oncogene. Our study indicates that the ets-1 oncogene is transposed in the t(11;19) translocation without detectable alteration at the DNA level. The absence of ets-1 amplification in t(11;19) and its presence in the t(4;11) and t(9;11) translocations demonstrated by others suggests the possible existence of different molecular mechanisms involving the ets-1 oncogene in the pathogenesis of these leukemias.     

Clinicopathological characteristics of acute lymphoblastic leukemia with the 4;11 chromosome translocation

Analysis of the bone marrow karyotype in 109 consecutive untreated patients with acute lymphoblastic leukemia (ALL) by the G-banding technique revealed the presence of a translocation between specific sites on the long arms of chromosomes 4 and 11, [t(4;11) (q21;q23)] in 3 adults and 2 children. Splenomegaly was present in all patients, marked leukocytosis in 4, and retinal hemorrhages in the absence of significant mucocutaneous bleeding in 3. Complete remission defined by conventional morphological criteria was achieved with combination chemotherapy in all instances, but the duration of remission was brief in 3. Three patients were studied in relapse, and clonal evolution was found to have occurred in 2. Analysis of our data in conjunction with other published reports suggests this specific karyotypic abnormality characterizes a small subgroup of ALL in which there is a strong association with recognized clinical and laboratory indices of poor prognosis, in particular its frequent occurrence in children under the age of 2.5 yr. There is a propensity to undergo clonal evolution, and the possibility exists that such a development is associated with poor prognosis.     

Dicentric translocation (9;12) presenting as refractory Philadelphia chromosome-positive acute B-cell lymphoblastic leukemia.

A 66-year-old Caucasian woman presented with a Philadelphia chromosome positive common B-cell acute lymphoblastic leukemia and a dic(9;12) involving the der(9)t(9;22), a rearrangement so far not observed in acute lymphoblastic leukemia. The patient was treated for the acute lymphoblastic leukemia, but showed refractory disease and died 6 months after initial diagnosis. This case suggests that, in the combination of t(9;22) and dic(9;12), the known poor prognostic feature of t(9;22) in acute lymphoblastic leukemia may outweigh the favorable outcome reported in patients with dic(9;12).     

Detection of t(12;21) in childhood acute lymphoblastic leukemia by fluorescence in situ hybridization

Metaphase preparations from 36 patients with acute lymphoblastic leukemia (ALL) have been retrospectively screened by fluorescence in situ hybridization (FISH) to determine the incidence of translocation (12;21) and the potential usefulness of FISH as an adjunct to conventional cytogenetic analysis. With the use of specific chromosome paints, 4 of 31 patients with B-lineage childhood ALL (13%) demonstrated rearrangements of chromosomes 12 and 21, and therefore, were considered to harbor the translocation, which had not previously been detected by conventional karyotyping. However, none of these positive cases revealed the standard reciprocal t(12;21)(p12;q22) as the sole abnormality involving chromosomes 12 and 21. The study confirms the feasibility and advantages of introducing FISH screening for t(12;21) in pediatric ALL cases and demonstrates the usefulness of FISH screening as a backup to concurrent cytogenetic analysis to resolve variant translocations and aberrant results. The presence of t(12;21) has also been correlated to clinical data to assess the prognostic significance of this translocation on its own or in association with other prognostic features.