Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with ANLL or MDS and abnormalities of the short arm of chromosome 12

Abstract

Summary. Abnormalities of the short arm of chromosome 12 (12p) are found in about 5% of acute nonlymphocytic leukaemias (ANLL) and myelodysplastic syndromes (MDS). They are described to be characteristic of secondary leukaemias, especially after prior mutagenic exposure, and to be associated with a poor prognosis. In our series of 59 patients with 12p abnormalities and ANLL or MDS, exposure to genotoxic agents was proven only in five patients, but in 13/44 patients ANLL evolved from an MDS. Patients with a small deletion del(12)(p11.2p13) having a mild clinical course were distinguished from those with a large del(12)(p11.2), additional chromosomal anomalies, and a poor clinical course. Among the 31 patients with translocations or dicentric chromosomes involving 12p, a group of eight with t/dic(12;13) was the most frequent and was associated with a poor prognosis. The clinical outcome was adverse in the majority of patients with complex karyotype abnormalities, but in some patients a milder clinical course seems likely. A new, hitherto undescribed, abnormality in an MDS case with a duplication dup(12)(p11.2p13) was the amplification of the signal of the yeast artificial chromosome (YAC) clone 964c10 (D12S736). In 38 cases with deletions or unbalanced translocations/dicentrics one YAC signal was lost. Five patients with balanced translocations demonstrated breakpoints within the YAC, containing the ETV6 (TEL) gene. The breakpoints were telomeric to the YAC 964c10 in seven cases and centromeric in one patient.

ETV6 deletion is a common additional abnormality in patients with myelodysplastic syndromes or acute myeloid leukemia and monosomy 7

“…Outside of two cohorts with chromosome 12 abnormalities 8,9 and one case series with complex karyotypes,…”

“…Cytogenetic information was available in 32 patients with 4 of 32 (12.5%) karyotypes conferring good, 21 of 32 (65.5%) intermediate, and 7 of 32 (22%) adverse risk. Median age at diagnosis was 55.5 years (range 18-80 years), median white blood cell (WBC) count 55.5x10 9 /L (range 5-445x10 9 /L). This cohort has also been characterized for RKIP expression, showing its loss in 17 of 36 (47%) patients as determined at protein and mRNA level using Western blot and quantitative real-time polymerase chain reaction (PCR), respectively.…”

Novel cryptic chromosomal rearrangements detected in acute lymphoblastic leukemia detected by application of new multicolor fluorescent in situ hybridization approaches

“…Thus, the cut-off for signal loss was determined at 2/20 mitosis. According to this definition, recurrent cryptic chromosomal aberrations were detected as terminal deletions in 12p13 [cases 3, 4, 5, 14, 15, 22, 24 and 25] Indications on involvement of 12p in ALL were previously found (31); interestingly in the present and in the previous study (31) no correlation with the ALL-subtype was detectable.…”

A 14.8 Mb 12p Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome

“…12p deletions are detected in a broad spectrum of hematological malignancies in acute myeloid leukemia (AML) they are usually associated with complex karyotypes, whereas in myelodysplastic syndromes these anomalies are often seen along with monosomy 7 [8][9][10][11]. Rucker et al showed that about half of the AML with complex karyotype (CK-AML) presented 12p13 deletions, when analyzed by high-resolution arrays [12].…”