11q23 rearrangements in childhood acute lymphoblastic leukemia

Identity

Note	Clinical aspects of 11q23 abnormalities in childhood acute lymphoblastic leukemia (ALL) are herein described.

Clinics and Pathology

Disease	Childhood acute lymphoblastic leukemia (11q23)
Note	Acute lymphoblastic leukemia (ALL) in infants is a clinically distinct entity from that diagnosed in older children. Infant ALL, which represents 3% of all cases of childhood ALL, is clinically aggressive and strongly associated with a poor prognosis. As mentioned below, leukemic cells in infants show preferential involvement of 11q23 chromosomal abnormalities / MLL gene rearrangements.
Phenotype / cell stem origin	Leukemic cells with 11q23 abnormalities, which include MLL gene rearrangements, are usually not hyperdiploid, have an early pre-B cell immunophenotype, and express myeloid antigens but not CD10. A few studies have found a strong association between 11q23 abnormalities and the expression of the human homolog of the rat chondroitin sulfate proteoglycan NG2. Therefore, the common immunophenotypes are CD19+, CD10-, CD15+, and/or CD65+, NG2+.
Etiology	There is strong molecular evidence that 11q23 abnormalities in infants with ALL occur in utero. The 11q23 band/MLL gene has an important role in normal hematopoietic growth and differentiation. Abnormalities in this region can occur very early in hematopoietic stem cell development. Indeed, in utero exposure to natural or synthetic substances that inhibit topoisomerase II (e.g., genistein, catechins, flavonoids) may result in acute leukemia. It has been suggested that rearrangement of the MLL gene leads to the inhibition of apoptosis and leukemogenesis.
Epidemiology	Depending on the method of detection, the incidence of 11q23 abnormalities among infants with ALL ranges from 60% to 80%. Among children who are older than 1 year and have ALL, the incidence of MLL gene rearrangements ranges from 4.5% to 5.7%. The t(4;11), one of the most common 11q23 abnormalities, occurs in 2% of children and adults with ALL. The following information was obtained from 2 published reports of a multinational collaborative study of 497 pediatric patients with 11q23 abnormalities and ALL. In this study, some data for a few patients were unavailable. Table 1. Frequency of five types of 11q23 abnormalities among three age groups of patients. 11q23 abnormality Total Number of patients (%)* - - <1 year old 1-9 years old >10 years old t(4;11) 252 149 (70) 58 (31) 45 (49) t(11;19) 49 27 (13) 12 (6) 10 (11) t(9;11) 19 8 (38) 10 (5) 1 (1) t(11q23;V) 77 23 (11) 44 (23) 10 (11) del(11q23) 94 5 (2) 64 (34) 25 (27) Total 491 212 (43) 188 (38) 91 (18) Abbreviation: V, variable chromosome *Percentage within the indicated age group.
Clinics	Children who have ALL and 11q23 abnormalities often experience organomegaly, high leukocyte counts, and involvement of the central nervous system (CNS) at the time of diagnosis. Table 2. The clinico-biological presenting features of 497 patients with ALL and 11q23/MLL rearrangement. 11q23 abnormality No. of Cases (%) Median Age in Years (range) Median WBC Counts, x 109/L (range) No. of patients with CNS involvement (%)* No. of patients with T-lineage ALL (%)** t(4;11) 256 (52) 0.65 (0.01-20.9) 224 (1-1400) 30 (12) 2 (0.8) t(11;19) 49 (10) 0.87 (0.03 - 16.7) 184 (3-1000) 5 (10) 8 (16) t(9;11) 20 ( 4) 1.46 (0.12 - 12.7) 51 (1-520) 4 (20) 0 t(11q23;V) 77 (15) 2.60 (0.02 - 15.1) 32 (2-1400) 8 (10) 17 (22) del(11q23) 95 (19) 5.34 (0.12 - 16.7) 14 (1-785) 5 (5) 13 (14) Abbreviations: V, indicates a variable chromosome *Fifty-two (11%) of 482 patients had CNS involvement. **Forty (8.7%) of 459 patients had T-lineage ALL.
Treatment	Because ALL in infants has distinctive biological characteristics and because infants have a high risk of leukemia recurrence, infants with ALL are usually treated on specifically designed protocols. Current intensified treatment approaches may offer better disease control in infants than do previously tested, less intensive approaches, but long-term outcome and toxicity are unknown. Leukemic cells from infants with ALL are significantly more resistant to prednisone and L-asparaginase in vitro than are leukemic cells from older patients with ALL. However, leukemic cells in infants are highly sensitive to cytosine arabinoside (ara-C). These findings were incorporated into two cooperative treatment protocols for infants with ALL: the international Interfant-99 protocol and a protocol of the Children's Oncology Group in the United States. New therapeutic regimens are needed to cure infants with 11q23 abnormalities and high-risk ALL. Recent studies have shown high levels of FLT3 expression in patients with MLL rearrangements; therefore, inhibitors of FLT3 (a tyrosine kinase) may prove to be beneficial.
Prognosis	The 11q23 abnormality/MLL gene rearrangement is generally associated with a high risk of treatment failure; in contrast, deletion or inversion of 11q23 is not. Although infants and adults with the t(4;11) are at higher risk of treatment failure, children aged 1 to 9 years appear to have a better outcome. For more details, see below Table 3. The impact of age and phenotype on the 5-year event-free survival (EFS) estimates for children with ALL and different types of 11q23 abnormality. Type of 11q23 abnormality Age, Lineage 5-year EFS, % (s.e.) P value t(4;11) <1 year, B lineage >1 year, B lineage 19 (3) 42 (5) <0.001 t(9;11) <1 year, B lineage >1 year, B lineage 38 (15) 46 (14) 0.27 t(11;19) <1 year, B lineage >1 year, B lineage T lineage 26 (8) 46 (14) 88 (13) 0.01 t(11q23;variable) <1 year, B lineage >1 year, B lineage 22 (8) 65 (7) <0.001 del(11)(q23) <1 year, B lineage >1 year, B lineage 40 (22) 73 (5) 0.05

Cytogenetics

Cytogenetics Morphological

t(4;11) The t(4;11) was the sole chromosomal abnormality in 200 (79%) of the 252 cases in which a t(4;11) was detected by conventional cytogenetics. The t(4;11) was observed in 41 cases that had other cytogenetic changes and in 11 cases that had variant translocations. In 4 cases, only molecular information (MLL-AF4+) was available. The t(4;11) was present in 70% (149/212) of infants, 31% (58/188) of children aged 1 to 9 years, and 49% (45/91) of patients aged 10 years or more. Infants with the t(4;11) had a worse outcome than did those who were older than 1 year (5-year event-free survival [EFS] estimates, 19% ± 3% vs. 42% ± 5%; P=0.0001). The outcome of infants with the t(4;11) and poor prednisone response (n=12) was dismal (5-year EFS estimate, 0%), whereas infants with the same abnormality and a good prednisone response (n=11) had a slightly better outcome (5-year EFS estimate, 23% ± 12%; P=0.0005). The outcome of infants who were younger than 3 months and had ALL and a t(4;11) was worse than that of infants who were older than 3 months and had ALL and the same chromosomal abnormality (5-year EFS estimates, 5% ± 5% vs. 23.4% ± 4%; P=0.0003). A poor prednisone response also appeared to confer a poor outcome for ALL patients 1 year of age or older with a t(4;11) (5-year EFS estimate, 33% ± 16%). ALL patients in the same age group and with a t(4;11) and a good prednisone response had a 5-year EFS estimate of 80% ± 18% (P=0.077). Leukocyte counts at initial examination had only a marginal prognostic impact for infants with t(4;11)-positive ALL and lacked significance for older pediatric patients in this genetic subgroup. In a retrospective analysis of 256 patients with the t(4;11) treated between 1983 and 1995, allogeneic stem cell transplantation provided no greater benefit than did intensive chemotherapy alone. t(11;19) The t(11;19) was the sole chromosomal abnormality in 31 (63%) of the 49 cases in which the t(11;19) was detected. In 15 cases (31%) with a t(11;19), additional changes were present, and in 3 additional cases, variant translocations were observed. The t(11;19) was found in 13% (27/212) of infants, 6% (12/188) of children aged 1 to 9 years, and in 11% (10/91) of children aged 10 years or more. Patients who had this translocation and were younger than 1 year had a worse outcome than did older patients (5-year EFS estimates, 26% ± 8% vs. 64% ± 12%; P=0.003). In the subgroup of infants with the t(11;19), age less than 6 months and female sex were associated with a poor treatment outcome; however, these findings from a multivariate analysis lacked statistical significance. None of the 26 infants with a t(11;19) had T-cell ALL, but this type of ALL was present in 8 (38%) of the 21 children who were older than 1 year and had a t(11;19). Of the patients with the t(11;19)(q23;p13.3) and the MLL-ENL fusion, those who had T-lineage ALL and were older than 1 year had a better outcome than did patients who had a t(11;19), were older than 1 year, and had B-lineage ALL (5-year EFS estimates, 88% ± 13% vs. 46% ± 14%, P=0.065). This finding confirmed previous observations. t(9;11) The t(9;11) was identified by RT-PCR only in 1 of 20 cases. Six (32%) of the other 19 cases had additional chromosomal changes; in 4 cases, a variant translocation was present. The t(9;11) was found in 3.8% (8/212) of infants, 5% (10/188) of children aged 1 to 9 years, and 1% (1/91) of patients aged 10 years or more. Age was not a predictor of outcome for infants with t(9;11)-positive ALL. Patients who had ALL and a t(9;11) and were younger than 1 year had a 5-year EFS estimate of 38% ± 15%, whereas those who had ALL and a t(9;11) and were older than 1 year had a 5-year EFS estimate of 46% ± 14% (P=0.27). t(11q23;variable) Of the 77 patients with a t(11q23;variable), 23 were infants. Southern blot analysis detected the abnormality in 6 infants. The t(11q23;variable) was found in 11% (23/212) of infants, 23% (44/188) of children aged 1 to 9 years, and 11% (10/91) of patients aged 10 years or more. The following recurrent chromosomal abnormalities were observed in 18 of the 23 infants: inv(11)(p15q23) (n=5), t(1;11)(p32;q23) (n=5), t(10;11)(p14-15;q23) (n=4), t(1;11)(q23;q23) (n=2) and t(10;11)(p13;q23) (n=2). For patients younger than 1 year who had the t(11q23;variable), the 5-year EFS estimate was 22% ± 8%, whereas those older than 1 year who also had this abnormality had a 5-year EFS estimate of 65% ± 7% (P<0.0001). del(11)(q23) The del(11)(q23) occurred in 2% (5/212) of infants, 34% (64/188) of children aged 1 to 9 years, and 27% (25/91) of patients aged 10 years or more. Only 5 infants had a del(11)(q23), and their treatment outcome was worse than that of 89 older children with the same abnormality (5-year EFS estimates, 40% ± 22% vs. 73% ± 5%; P=0.05). Although patients with the del(11)(q23) were a very heterogeneous group, the National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance: the 5-year EFS estimate was 64% ± 8% for patients with high-risk disease and 83% ± 6% for those with standard-risk disease (P=0.04). The findings from the international collaborative study can be summarized as follows: Only age at initial treatment had a significant effect on EFS estimates of pediatric patients with ALL and 11q23 abnormalities. Infants (n=212) uniformly fared worse than children aged 1 to 9 years (n=188) and those aged 10 years or more (n=91). Furthermore, when the two groups of older patients were further divided by type of 11q23 abnormalities, each group had a similar outcome. Irrespective of the 11q23 abnormality, infants had a worse treatment outcome than did older patients. Any category of 11q23 abnormality conferred a dismal outcome for infants, whereas in older patients the t(4;11) (n=103) and the t(9;11) (n=22) were associated with an outcome worse than that associated with other 11q23 changes. The t(4;11) and the t(11;19) were usually found in the youngest children, whereas the del(11)(q23) was typically detected in the oldest. The t(4;11) and the t(9;11) were rarely found in patients with T-lineage leukemia. Patients with the t(4;11) or the t(11;19) were most likely to belong to the high-risk group defined by the National Cancer Institute-Rome criteria, whereas those with the del(11)(q23) were the least likely. T-lineage ALL was present in 40 (8.7%) of the 459 cases in which the leukemic cells' immunophenotype was known. CNS involvement was observed in 12% (52/430) of patients with 11q23 abnormalities. For patients with the t(4;11), any type of transplantation, including allogeneic transplantation of hematopoietic stem cells from an HLA-matched related or unrelated donor, was associated with significantly a worse disease-free survival estimate than was chemotherapy alone.

Cytogenetics Molecular

Some MLL gene rearrangements are not detected by conventional cytogenetic methods. The commercially available dual-color MLL probe (Vysis, Inc., Downers Grove, IL, USA) allows FISH evaluation of derivatives of an MLL translocation in metaphase chromosomes and the splitting of the hybridizing probe's signal in interphase nuclei. In rare instances, this probe detects not only the reciprocal translocation but also a deletion of at least 190 kb from the 3' region of the MLL gene. Molecular cytogenetic methods have shown that the frequency of MLL gene rearrangements exceeds that of 11q23 translocations detected by conventional cytogenetic methods. In ALL cases in which deletions and inversions affect the 11q23 band (both types of abnormality are associated with favorable clinical features and prognoses), FISH should be done to determine whether a cryptic rearrangement of MLL is present. In a few cases, an 11q23 translocation involves genes other than MLL. Because the translocation partners for 11q23 are markedly heterogeneous, additional molecular methods are needed to further assess the MLL gene in patients with an 11q23 abnormality. Information from such assessments can then be used to better stratify treatment groups.

Bibliography

Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.

Pui CH, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, Crist WM, Land VJ, Pullen DJ, Steuber CP

Blood. 1991 ; 77 (3) : 440-447.

PMID 1991161

Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome.

Chen CS, Sorensen PH, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA, Hammond GD, Kersey JH

Blood. 1993 ; 81 (9) : 2386-2393.

PMID 8481519

In utero rearrangements in the trithorax-related oncogene in infant leukaemias.

Ford AM, Ridge SA, Cabrera ME, Mahmoud H, Steel CM, Chan LC, Greaves M

Nature. 1993 ; 363 (6427) : 358-360.

PMID 8497319

Current status of cytogenetic research in childhood acute lymphoblastic leukemia.

Raimondi SC

Blood. 1993 ; 81 (9) : 2237-2251.

PMID 8481506

Improved survival for acute lymphoblastic leukaemia in infancy: the experience of EORTC-Childhood Leukaemia Cooperative Group.

Ferster A, Bertrand Y, Benoit Y, Boilletot A, Behar C, Margueritte G, Thyss A, Robert A, Mazingue F, Souillet G

British journal of haematology. 1994 ; 86 (2) : 284-290.

PMID 8199016

11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.

Pui CH, Behm FG, Downing JR, Hancock ML, Shurtleff SA, Ribeiro RC, Head DR, Mahmoud HH, Sandlund JT, Furman WL

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994 ; 12 (5) : 909-915.

PMID 8164041

Childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): an update.

Pui CH, Carroll LA, Raimondi SC, Shuster JJ, Crist WM, Pullen DJ

Blood. 1994 ; 83 (8) : 2384-2385.

PMID 8161808

ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells.

Rubnitz JE, Morrissey J, Savage PA, Cleary ML

Blood. 1994 ; 84 (6) : 1747-1752.

PMID 8080983

Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias.

Cimino G, Rapanotti MC, Rivolta A, Lo Coco F, D'Arcangelo E, Rondelli R, Basso G, Barisone E, Rosanda C, Santostasi T

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1995 ; 9 (3) : 391-395.

PMID 7885037

Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(p13q23) lack MLL gene rearrangements and have favorable clinical features.

Raimondi SC, Frestedt JL, Pui CH, Downing JR, Head DR, Kersey JH, Behm FG

Blood. 1995 ; 86 (5) : 1881-1886.

PMID 7655016

Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age.

Behm FG, Raimondi SC, Frestedt JL, Liu Q, Crist WM, Downing JR, Rivera GK, Kersey JH, Pui CH

Blood. 1996 ; 87 (7) : 2870-2877.

PMID 8639906

Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements.

Behm FG, Smith FO, Raimondi SC, Pui CH, Bernstein ID

Blood. 1996 ; 87 (3) : 1134-1139.

PMID 8562939

The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not expressed on the cell surface of normal hematopoietic cells but is expressed by acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of chromosome band 11q23.

Smith FO, Rauch C, Williams DE, March CJ, Arthur D, Hilden J, Lampkin BC, Buckley JD, Buckley CV, Woods WG, Dinndorf PA, Sorensen P, Kersey J, Hammond D, Bernstein ID

Blood. 1996 ; 87 (3) : 1123-1133.

PMID 8562938

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, Gelber R, Heerema N, Korn EL, Link M, Murphy S, Pui CH, Pullen J, Reamon G, Sallan SE, Sather H, Shuster J, Simon R, Trigg M, Tubergen D, Uckun F, Ungerleider R

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1996 ; 14 (1) : 18-24.

PMID 8558195

Therapeutic trial for infant acute lymphoblastic leukemia: the Pediatric Oncology Group experience (POG 8493).

Frankel LS, Ochs J, Shuster JJ, Dubowy R, Bowman WP, Hockenberry-Eaton M, Borowitz M, Carroll AJ, Steuber CP, Pullen DJ

Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 1997 ; 19 (1) : 35-42.

PMID 9065717

Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.

Gale KB, Ford AM, Repp R, Borkhardt A, Keller C, Eden OB, Greaves MF

Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (25) : 13950-13954.

PMID 9391133

Intensified therapy for infants with acute lymphoblastic leukemia: results from the Dana-Farber Cancer Institute Consortium.

Silverman LB, McLean TW, Gelber RD, Donnelly MJ, Gilliland DG, Tarbell NJ, Sallan SE

Cancer. 1997 ; 80 (12) : 2285-2295.

PMID 9404706

Hematological malignancies with a deletion of 11q23: cytogenetic and clinical aspects. European 11q23 Workshop participants.

Harbott J, Mancini M, Verellen-Dumoulin C, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 823-827.

PMID 9593287

Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.

Harrison CJ, Cuneo A, Clark R, Johansson B, Lafage-Pochitaloff M, Mugneret F, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 811-822.

PMID 9593286

Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants.

Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 779-787.

PMID 9593281

Intensive alternating drug pairs after remission induction for treatment of infants with acute lymphoblastic leukemia: A Pediatric Oncology Group Pilot Study.

Lauer SJ, Camitta BM, Leventhal BG, Mahoney D Jr, Shuster JJ, Kiefer G, Pullen J, Steuber CP, Carroll AJ, Kamen B

Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 1998 ; 20 (3) : 229-233.

PMID 9628434

The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.

Lillington DM, Young BD, Berger R, Martineau M, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 801-804.

PMID 9593284

The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. European 11q23 Workshop participants.

Moorman AV, Hagemeijer A, Charrin C, Rieder H, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 805-810.

PMID 9593285

Relation between age, immunophenotype and in vitro drug resistance in 395 children with acute lymphoblastic leukemia--implications for treatment of infants.

Pieters R, den Boer ML, Durian M, Janka G, Schmiegelow K, Kaspers GJ, van Wering ER, Veerman AJ

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (9) : 1344-1348.

PMID 9737681

Acute lymphoblastic leukemia.

Pui CH, Evans WE

The New England journal of medicine. 1998 ; 339 (9) : 605-615.

PMID 9718381

A multiplex RT-PCR assay for the detection of chimeric transcripts encoded by the risk-stratifying translocations of pediatric acute lymphoblastic leukemia.

Scurto P, Hsu Rocha M, Kane JR, Williams WK, Haney DM, Conn WP, Shurtleff SA, Downing JR

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (12) : 1994-2005.

PMID 9844930

Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants.

Swansbury GJ, Slater R, Bain BJ, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 792-800.

PMID 9593283

Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia.

Dˆrdelmann M, Reiter A, Borkhardt A, Ludwig WD, Gˆtz N, Viehmann S, Gadner H, Riehm H, Schrappe M

Blood. 1999 ; 94 (4) : 1209-1217.

PMID 10438708

Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11) - a report of the Children's Cancer Group.

Heerema NA, Sather HN, Ge J, Arthur DC, Hilden JM, Trigg ME, Reaman GH

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 ; 13 (5) : 679-686.

PMID 10374870

Comparison of cytogenetics, Southern blotting, and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in children with acute leukemia and with 11q23 abnormalities.

Mathew S, Behm F, Dalton J, Raimondi S

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 ; 13 (11) : 1713-1720.

PMID 10557043

Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821.

Raimondi SC, Chang MN, Ravindranath Y, Behm FG, Gresik MV, Steuber CP, Weinstein HJ, Carroll AJ

Blood. 1999 ; 94 (11) : 3707-3716.

PMID 10572083

Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group.

Reaman GH, Sposto R, Sensel MG, Lange BJ, Feusner JH, Heerema NA, Leonard M, Holmes EJ, Sather HN, Pendergrass TW, Johnstone HS, O'Brien RT, Steinherz PG, Zeltzer PM, Gaynon PS, Trigg ME, Uckun FM

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (2) : 445-455.

PMID 10080584

Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation.

Rubnitz JE, Camitta BM, Mahmoud H, Raimondi SC, Carroll AJ, Borowitz MJ, Shuster JJ, Link MP, Pullen DJ, Downing JR, Behm FG, Pui CH

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (1) : 191-196.

PMID 10458233

Biological and therapeutic aspects of infant leukemia.

Biondi A, Cimino G, Pieters R, Pui CH

Blood. 2000 ; 96 (1) : 24-33.

PMID 10891426

Identification and molecular characterization of CALM/AF10fusion products in T cell acute lymphoblastic leukemia and acute myeloid leukemia.

Carlson KM, Vignon C, Bohlander S, Martinez-Climent JA, Le Beau MM, Rowley JD

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (1) : 100-104.

PMID 10637483

Treatment outcome in infant acute lymphoblastic leukemia. Children Leukemia Cooperative Group--EORTC. European Organization for Research and Treatment of Cancer.

Ferster A, Benoit Y, Francotte N, Dresse MF, Uyttebroeck A, Plouvier E, Thyss A, Lutz P, Marguerite G, Behar C, Mazingue F, Boutard P, Millot F, Rialland X, Mechinaud F, Norton L, Robert A, Otten J, Vilmer E, Philippe N, Waterkeyn C, Suciu S

Blood. 2000 ; 95 (8) : 2729-2731.

PMID 10809540

The Atlas of genetics and cytogenetics in oncology and haematology on the internet and a review on infant leukemias.

Huret JL, Dessen P, Le Minor S, Bernheim A

Cancer genetics and cytogenetics. 2000 ; 120 (2) : 155-159.

PMID 10942808

Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion.

Alexander FE, Patheal SL, Biondi A, Brandalise S, Cabrera ME, Chan LC, Chen Z, Cimino G, Cordoba JC, Gu LJ, Hussein H, Ishii E, Kamel AM, Labra S, Magalhˆ£es IQ, Mizutani S, Petridou E, de Oliveira MP, Yuen P, Wiemels JL, Greaves MF

Cancer research. 2001 ; 61 (6) : 2542-2546.

PMID 11289128

Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol.

Hann I, Vora A, Harrison G, Harrison C, Eden O, Hill F, Gibson B, UK Medical Research Council's Working Party on Childhood Leukaemia, Richards S

British journal of haematology. 2001 ; 113 (1) : 103-114.

PMID 11328289

An atlas of chromosomes in hematological malignancies. Example: 11q23 and MLL partners.

Huret JL, Dessen P, Bernheim A

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (6) : 987-989.

PMID 11417488

Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis.

Kolomietz E, Al-Maghrabi J, Brennan S, Karaskova J, Minkin S, Lipton J, Squire JA

Blood. 2001 ; 97 (11) : 3581-3588.

PMID 11369654

Molecular tracking of leukemogenesis in a triplet pregnancy.

Maia AT, Ford AM, Jalali GR, Harrison CJ, Taylor GM, Eden OB, Greaves MF

Blood. 2001 ; 98 (2) : 478-482.

PMID 11435320

Molecular tracking of leukemogenesis in a triplet pregnancy.

Maia AT, Ford AM, Jalali GR, Harrison CJ, Taylor GM, Eden OB, Greaves MF

Blood. 2001 ; 98 (2) : 478-482.

PMID 11435320

Restricted chromosome breakpoint sites on 11q22-q23.1 and 11q25 in various hematological malignancies without MLL/ALL-1 gene rearrangement.

Tanaka K, Eguchi M, Eguchi-Ishimae M, Hasegawa A, Ohgami A, Kikuchi M, Kyo T, Asaoku H, Dohy H, Kamada N

Cancer genetics and cytogenetics. 2001 ; 124 (1) : 27-35.

PMID 11165319

MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.

Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, Sallan SE, Lander ES, Golub TR, Korsmeyer SJ

Nature genetics. 2002 ; 30 (1) : 41-47.

PMID 11731795

Infant acute lymphoblastic leukemia - combined cytogenetic, immunophenotypical and molecular analysis of 77 cases.

Borkhardt A, Wuchter C, Viehmann S, Pils S, Teigler-Schlegel A, Stanulla M, Zimmermann M, Ludwig WD, Janka-Schaub G, Schrappe M, Harbott J

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (9) : 1685-1690.

PMID 12200682

Molecular analysis of an unusual rearrangement between chromosomes 4 and 11 in adult pre-B-cell acute lymphoblastic leukemia.

Chami I, Pˆ©rot C, PortnoˆØ MF, Jouault H, Rieux C, Pautas C, Kuentz M, Tulliez M, Bories D

Cancer genetics and cytogenetics. 2002 ; 133 (2) : 129-133.

PMID 11943339

Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party.

Chessells JM, Harrison CJ, Kempski H, Webb DK, Wheatley K, Hann IM, Stevens RF, Harrison G, MRC Childhood Leukaemia working party, Gibson BE

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (5) : 776-784.

PMID 11986937

Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987-1999.

Chessells JM, Harrison CJ, Watson SL, Vora AJ, Medical Research Council Working Party on Childhood Leukaemia, Richards SM

British journal of haematology. 2002 ; 117 (2) : 306-314.

PMID 11972512

Two new translocations involving the 11q23 region map outside the MLL locus in myeloid leukemias.

Giugliano E, Rege-Cambrin G, Scaravaglio P, Wlodarska I, Emanuel B, Stul M, Serra A, Tonso A, Pini M, Saglio G, Hagemeijer A

Haematologica. 2002 ; 87 (10) : 1014-1020.

PMID 12368154

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).

Isoyama K, Eguchi M, Hibi S, Kinukawa N, Ohkawa H, Kawasaki H, Kosaka Y, Oda T, Oda M, Okamura T, Nishimura S, Hayashi Y, Mori T, Imaizumi M, Mizutani S, Tsukimoto I, Kamada N, Ishii E

British journal of haematology. 2002 ; 118 (4) : 999-1010.

PMID 12199778

A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo.

Levis M, Allebach J, Tse KF, Zheng R, Baldwin BR, Smith BD, Jones-Bolin S, Ruggeri B, Dionne C, Small D

Blood. 2002 ; 99 (11) : 3885-3891.

PMID 12010785

Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region.

Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, Silverman LB, Biondi A, Harms DO, Vilmer E, Schrappe M, Camitta B

Lancet. 2002 ; 359 (9321) : 1909-1915.

PMID 12057554

Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification.

Armstrong SA, Kung AL, Mabon ME, Silverman LB, Stam RW, Den Boer ML, Pieters R, Kersey JH, Sallan SE, Fletcher JA, Golub TR, Griffin JD, Korsmeyer SJ

Cancer cell. 2003 ; 3 (2) : 173-183.

PMID 12620411

Cryptic rearrangement involving MLL and AF10 occurring in utero.

Jones LK, Neat MJ, van Delft FW, Mitchell MP, Adamaki M, Stoneham SJ, Patel N, Saha V

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (8) : 1667-1669.

PMID 12886258

Treatment by design in leukemia, a meeting report, Philadelphia, Pennsylvania, December 2002.

Larson RA, Daley GQ, Schiffer CA, Porcu P, Pui CH, Marie JP, Steelman LS, Bertrand FE, McCubrey JA

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (12) : 2358-2382.

PMID 14562120

Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.

Pui CH, Chessells JM, Camitta B, Baruchel A, Biondi A, Boyett JM, Carroll A, Eden OB, Evans WE, Gadner H, Harbott J, Harms DO, Harrison CJ, Harrison PL, Heerema N, Janka-Schaub G, Kamps W, Masera G, Pullen J, Raimondi SC, Richards S, Riehm H, Sallan S, Sather H, Shuster J, Silverman LB, Valsecchi MG, Vilmer E, Zhou Y, Gaynon PS, Schrappe M

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (4) : 700-706.

PMID 12682627

Contributor(s)

Written	02-2004	Susana C Raimondi
		Director of Cytogenetics Laboratory, Department of Pathology (Room 4023A), St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA

Citation

This paper should be referenced as such :

Raimondi SC . 11q23 rearrangements in childhood acute lymphoblastic leukemia. Atlas Genet Cytogenet Oncol Haematol. February 2004 . URL : http://AtlasGeneticsOncology.org/Anomalies/11q23ChildALLID1321.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon May 12 18:11:06 2008

For comments and suggestions or contributions, please contact us