Detection of 16 p deletions by FISH in patients with inv(16) or t(16;16) and acute myeloid leukemia (AML)

Abstract

for the relatively favorable outcome in this group. However, Keywords: inv(16)(p13q22); t(16;16)(p13;q22); 16 p deletions; FISH; acute myeloid leukemia; prognosis in another study, no difference in prognosis was observed between deletion and non-deletion patients. 18 To assess further the incidence of the 16 p deletions and to improve the understanding of their prognostic significance, we Introduction studied 15 patients with AML and inv(16) or t(16;16) by fluorescence in situ hybridization (FISH) using the zit14 cosmid In 1983, Arthur and Bloomfield 1,2 reported five patients with as a probe. Clinical, cytogenetic and FISH data are reported acute myeloid leukemia (AML) of myelomonocytic type (M4), here. increased marrow eosinophils and a structurally abnormal chromosome 16. Soon after, a pericentric inversion of chromosome 16, inv(16)(p13q22), was described in 18 patients Patients, materials and methods who had M4 leukemia and morphologically abnormal eosinophils with irregular, basophilic-staining granules and distinct Patients cytochemical properties. 3,4 A related chromosome abnormality, t(16;16)(p13;q22), was reported in one patient with Fifteen patients with either inv(16) or t(16;16) were diagnosed similar characteristics. 5 Further studies have suggested that at the divisions of hematology of the University Hospitals of these two abnormalities were uniquely associated with M4 Zü rich (four patients), Basel (three), Bern (three), Lausanne and abnormal eosinophils and the correlation between the (two) and of the Canton Hospitals of Sankt-Gallen (two) and karyotype and morphology has led to a subcategory in the Aarau (one) between 1992 and 1995 (Table 1). Each patient FAB classification, namely M4Eo. 6 However, both rearrangewas assigned a unique patient number for this and previous ments have been reported in other types of myeloid dispublications. [19][20][21] Additionally, 10 patients with AML (nine) or orders. 7,8 In most studies, the presence of inv(16)/t(16;16) has acute lymphoblastic leukemia (ALL) (one) and normal karyobeen associated with a high cure rate with standard chemotypes or aberrations other than inv(16) or t(16;16) were investitherapy and a relatively favorable prognosis. [9][10][11][12][13] gated by FISH and served as controls. Informed consent was Inv(16) and t(16;16) have been shown to involve, on 16p13, obtained from each patient. a smooth muscle myosin heavy chain gene (MYH11) and, onThe diagnosis and classification of patients were based on morphologic and cytochemical examination of peripheral blood (PB) films, bone marrow (BM) aspirate and biopsy speci-

Deletion of the multidrug resistance-associated protein (MRP1) gene in acute myeloid leukemia with inversion of chromosome 16 has no prognostic impact

“…Furthermore, time to treatment failure was compared for the two patient groups and no difference was observed. Similar results were also reported in a study from Martinet et al 5 One drawback of all these studies is that the analyses were performed retrospectively in small series of patients treated heterogenously.…”

“…Furthermore, time to treatment failure was compared for the two patient groups and no difference was observed. Similar results were also reported in a study from Martinet et al 5 One drawback of all these studies is that the analyses were performed retrospectively in small series of patients treated heterogenously.To prospectively evaluate the prognostic impact of MRP1 deletions in AML with inv(16) we analyzed 246 eligible AML patients treated within the German multicenter treatment trial AML HD93 conducted between 1993 and 1998. All patients received induction therapy consisting of two cycles of idarubicin, cytarabine (100 mg/m 2 ), and etoposide (ICE), followed by first consolidation treatment with high-dose cytarabine (3 g/m 2 × 6) and mitoxantrone (HAM).…”

“…2 Recently, deletions of sequences 150 to 350 kb in size centromeric to the p-arm breakpoint were described in subsets of 14% to 38% of AMLs with inv(16). [3][4][5][6] The affected genomic region contains two members of the superfamily of transmembrane transporters, the multidrug resistance-associated protein gene (MRP1) and the anthracycline resistance-associated gene (ARA), located within 9 kb of each other. Both genes are expressed in normal hematopoietic precursor cells and mediate resistance to a variety of chemotherapeutic agents.…”

Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients

“…22 As seen in two patients, these two-color FISH assays also identified the cryptic del(16p), previously reported to have an incidence between 18 and 33% of inv(16) cases. 9,10 In our series, however, the incidence of del(16p) was lower (9%) than that reported, but this may be explained by patient selection, mainly based on the occurrence of a clinical relapse.…”

“…Moreover, CC cannot detect cryptic deletions of sequences centromeric to the p-arm breakpoint which have been described in a subset of inv(16) AML patients, accounting for 18-33% of cases. [7][8][9][10] The RT-PCR is able to detect CBF␤/MYH11 fusion transcript in the majority of inv(16)-positive cases at diagnosis; however, some cases remain RT-PCR negative. This finding might be caused by the diversity among inv(16) chimeric transcripts, together with the presence of alternatively spliced transcripts or poor quality RNA.…”