Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities

Secker-Walker, LM; Moorman, AV; Bain, BJ; Mehta, A

doi:10.1038/sj.leu.2401021

Cited by 106 publications

(74 citation statements)

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“…56,57 A review of the literature, however, reveals that all published therapy-associated t(4;11)-positive ALL, in which treatment was specified, had received chemotherapy targeting DNA topoisomerase II, ie etoposide, teniposide, doxorubicin, epidoxorubicin and mitoxantrone. 5 A detailed discussion on therapy-related 11q23 malignancies collected by the Workshop, including the present 10 cases, is found in Secker-Walker et al 58 The majority of the 183 cases of leukemia displayed t(4;11) as the sole change; additional, or secondary, changes were seen in only 30% of the cases (Table 1). Previous studies have also shown that t(4;11) usually occurs as the sole anomaly.…”

Section: Discussionmentioning

confidence: 85%

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

et al. 1998

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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.

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Section: Discussionmentioning

confidence: 85%

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

et al. 1998

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“…The median white blood cell count (WBC) (×10 9 /l) and percentage of blasts in the bone marrow were 58.1 and 50, respectively, for the infants, 44.3 and 90, respectively, for the children and 32 and 95, respectively, for the adults. One patient had a secondary, therapy-related AML, an adult who had received lumbar irradiation, 12 the remainder of patients presented with de novo disease.…”

Section: Patient Data At Diagnosismentioning

confidence: 99%

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

Lillington

Young

Berger³

et al. 1998

Leukemia

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The clinical, haematological and cytogenetic data for 20 patients with an acquired abnormality of 11q23 and 10p have been reviewed at this workshop. Patients predominantly presented with de novo AML M5a and the most common cytogenetic finding was an inversion of part of the long arm of chromosome 11 followed by a translocation between 11q and 10p. Band p12 represented the most common breakpoint on chromosome 10. The t(10;11) subgroup defined a subset of younger 11q23 patients, the majority of whom achieve a first complete remission despite the differing treatment regimens.

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“…MLL fusion genes are found in precursor-B-ALL, AML, myelodysplastic syndrome (MDS), some cases of T-ALL, and in secondary leukemia. [60][61][62][63][64][65][66] In addition to MLL fusion genes generated by translocations, deletions of exon 11 have been associated with T-ALL 67 and tandem duplications of the gene have been observed in both de novo and secondary AML 68 as well as in normal peripheral blood and bone marrow mononuclear cells. 69 The AF4 gene is composed of 20 exons and encodes a serine-proline-rich protein.…”

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1999

Leukemia

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Prospective studies on the detection of minimal residual disease (MRD) in acute leukemia patients have shown that largescale MRD studies are feasible and that clinically relevant MRDbased risk group classification can be achieved and can now be used for designing new treatment protocols. However, multicenter international treatment protocols with MRD-based stratification of treatment need careful standardization and quality control of the MRD techniques. This was the aim of the European BIOMED-1 Concerted Action 'Investigation of minimal residual disease in acute leukemia: international standardization and clinical evaluation' with participants of 14 laboratories in eight European countries (ES, NL, PT, IT, DE, FR, SE and AT). Standardization and quality control was performed for the three main types of MRD techniques, ie flow cytometric immunophenotyping, PCR analysis of antigen receptor genes, and RT-PCR analysis of well-defined chromosomal aberrations. This study focussed on the latter MRD technique. A total of nine well-defined chromosome aberrations with fusion gene transcripts were selected: t(1;19) with E2A-PBX1, t(4;11) with MLL-AF4, t(8;21) with AML1-ETO, t(9;22) with BCR-ABL p190 and BCR-ABL p210, t(12;21) with TEL-AML1, t(15;17) with PML-RARA, inv (16) with CBFB-MYH11, and microdeletion 1p32 with SIL-TAL1. PCR primers were designed according to predefined criteria for single PCR (external primers A ↔ B) and nested PCR (internal primers C ↔ D) as well as for 'shifted' PCR with a primer upstream (E5Ј primer) or downstream (E3Ј primer) of the external A ↔ B primers. The 'shifted' E primers were designed for performing an independent PCR together with one of the internal primers for confirmation (or exclusion) of positive results. Various local RT and PCR protocols were compared and subsequently a common protocol was designed, tested and adapted, resulting in a standardized RT-PCR protocol. After initial testing (with adaptations whenever necessary) and approval by two or three laboratories, the primers were tested by all participating laboratories, using 17 cell lines and patient samples as positive controls. This testing included comparison with local protocols and primers as well as sensitivity testing via dilution experiments. The collaborative efforts resulted in standardized primer sets with a minimal target sensitivity of 10 −2 for virtually all single PCR analyses, whereas the nested PCR analyses generally reached the minimal target sensitivity of 10 −4 . The standardized RT-PCR protocol and primer sets can now be used for molecular classification of acute leukemia at diagnosis and for MRD detection during follow-up to evaluate treatment effectiveness. Keywords: acute myeloid leukemia (AML); acute lymphoblastic leukemia (ALL); PCR; standardization; fusion genes; chromosome PrefaceMonitoring of acute leukemia patients during and after treatment for the presence of remaining leukemic cells ('minimal residual disease', MRD) has been shown to give major insight into the effectiveness of treatment. [1...

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Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities

Cited by 106 publications

References 20 publications

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

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

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

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