Hematologic malignancies with t(4;11)(q21;q23) – a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases

Abstract

A total of 183 hematologic malignancies with t(4;11)(q21;q23), including five variant translocations, were collected by the Workshop. Clinical, morphologic and immunophenotypic features were compiled, and karyotypes with variant t(4;11) or secondary chromosomal aberrations were reviewed. All cases were acute leukemias (AL): 173 acute lymphoblastic leukemias (ALL), six acute myeloid leukemias (AML), three unclassifiable AL, and one biphenotypic AL. Ten patients had treatment-associated AL. Females were overrepresented (104 vs 79) and the age distribution was clearly nonrandom; 34% of the cases occurred in infants below the age of 12 months. The remaining AL were evenly distributed among the other age groups, with the oldest patient being 79 years old. An increased white blood cell count (WBC) was reported in more than 90% of the cases, with hyperleukocytosis (у100 × 10 9 /l) in 64%. Additional chromosomal changes were detected in 55 (30%) cases, most often gain of the X chromosome, i(7)(q10), and trisomy 8, with frequent breakpoints in 1p36, 1q21, 7q10, 11p15, 12p13, 17p11, and 17p10. All recurrent secondary changes resulted in genomic imbalances, in particular gains of 1q, 7q, 8, and X and losses of 7p and 17p. Event-free and overall survival (EFS and OS) could be ascertained in 170 and 171 patients, respectively. Kaplan-Meier estimates of EFS and OS showed no differences with regard to gender, WBC, or presence of secondary chromosomal abnormalities, and there was no increase of EFS or OS among the 55 cases that had undergone bone marrow transplantation. However, age had an important prognostic impact, with significantly (P Ͻ 0.0001) longer EFS and OS in children 2-9 years old than among infants and younger children, patients aged between 10 and 39 years and older adults.

Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10−/CD24−/CD65s+/CD15+ B-cell phenotype

“…This parallels findings from the European Union Concerted Action Workshop on 11q23: among ALL patients with t(4;11)(q21;q23) 15% (26/173) were classified as pre-B ALL and del(11)(q23) has also been demonstrated in pre-B-ALL. 22,23 Thus, the close association between NG2 positivity and the presence of MLL rearrangement in these nine patients with pre-B-ALL strongly suggest that these patients are at an increased risk for treatment failure. The fact that none of our patients with mature B-ALL and T-ALL showed NG2 expression corresponds to previous findings.…”

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

“…4,70 The t(4;11)(q21;q23) and t(11;19)(q23;p13.3) are the most common translocations in ALL, whereas t(6;11)(q27;q23), t(9;11)(p21-p22;q23), t(10;11)(p12;q23), and t(11;19)(q23;p13.1) are most frequent in AML. [71][72][73][74][75][76] The MLL gene is the human homologue of the Drosophila trithorax gene. 77 The MLL protein contains a transcription repression domain, a transcription activation domain, and two types of DNA-binding domains (minor groove DNA-binding 'AT-hook' motifs and major groove DNA-binding zinc-fingers).…”

International childhood Acute Lymphoblastic Leukemia workshop: Sausalito, CA, 30 November–1 December 2000

“…Among B-lineage ALL cases with the t(4;11)(q21;q23) or t(11;19)(q23;p13.3), infants less than 12 months of age have a poor outcome, whereas those 1 to 9 years old have a relatively favorable prognosis. [24][25][26] A limited study suggested that prednisone response can further discriminate two prognostic groups among infants with the t(4;11). 27 However, neither bone marrow nor peripheral blood response after 8 days of remission induction therapy with prednisone, vincristine, daunorubicin and asparaginase, was predictive of event-free survival among 51 infants treated on a recent Medical Research Council (MRC) infant ALL protocol.…”