Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO‐93‐AML trial between 1993 and 2001

Abstract

Summary. Between 1993 and 2001, 318 children were diagnosed with acute myeloid leukaemia (AML) in the Nordic countries. The patient group comprised 237 children < 15 years of age with de novo AML, 42 children < 15 years with Down syndrome (DS) and de novo AML, 18 adolescents 15-18 years of age with de novo AML, and 21 children < 15 years with treatment-related AML (t-AML). The first group was all-inclusive, yielding an annual childhood de novo AML incidence of 0AE7/100 000. Cytogenetic analyses were successful in 288 cases (91%), and clonal chromosomal abnormalities were detected in 211 (73%). The distribution of ploidy levels were pseudodiploidy (55%), hyperdiploidy (34%) and hypodiploidy (11%). The most common aberrations (> 2%) were + 8 (23%) (as a sole change in 6AE2%), 11q23-translocations, including cryptic MLL rearrangements (22%) [t(9;11)(p21-22;q23) in 11%], t(8;21)(q22;q22) (9AE0%), inv(16)(p13q22) (6AE2%), )7/7q-(5AE2%), and t(15;17)(q22;q12) (3AE8%). Except for +8, these abnormalities were rare in group 2; only one DS patient had a t(8;21) and none had 11q23-translocations, t(15;17) or inv(16). In the t-AML group, three cases displayed 11q23-rearrangements, all t(9;11); and there were no t(8;21), t(15;17) or inv(16). Overall, the observed frequencies of t(8;21) and t(15;17) were lower, and frequencies of trisomy 8 and 11q23-translocations higher, than in previous studies. Furthermore, seven abnormalities that were previously reported as only single AML cases were also seen, meaning that der(4)t(4;11)(q26-27;q23), der(6)t(1;6)(q24-25;q27), der(7)t(7;11)(p22;q13), inv(8)(p23q11-12), t(11;17)(p15;q21), der(16)t(10;16)(q22;p13) and der(22)t(1;22)(q21;q13) are now classified as recurrent abnormalities in AML. In addition, 37 novel aberrations were observed, 11 of which were sole anomalies.

Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study

“…Future global gene expression analyses should be able to clarify whether there are significant differences in expression patterns of CEBP gene family members between DS-ALL and non-DS-ALL. Regarding AML, and in line with several previous studies, 4,29,34,38,39 the present compilation clearly revealed that t(8;21), 11q23 translocations, and inv(16) are significantly less common in DS-AML than in non-DS-AML (Table 2). Furthermore, none of the 136 DS-AMKL harbored the t(1;22), verifying that this translocation is very rare indeed in this AML type.…”

“…Not surprisingly, frequent gain of this chromosome has been found in most previous studies of DS-AML. 4,10,15,29,38,[40][41][42][43][45][46][47] Less well appreciated is the fact that ϩ8 often is the sole acquired anomaly in DS-AML, being found in 30% of the cases with single anomalies. Thus, this abnormality is undoubtedly intimately involved in the leukemogenesis of DS-AML.…”

“…Consistent with the distinct genetic nature of DS-AML, several studies have reported that they seldom harbor the characteristic AML-related aberrations inv(3)(q21q26), t(8;21)(q22;q22), MLL rearrangements, t(15;17)(q22;q21), and inv(16)(p13q22); furthermore, the t(1;22)(p13;q13), which encodes the chimeric RBM15/MKL1 transcript and that is characteristic for infant AMKL, is rarely found in DS-AMKL. 4,10,15,[29][30][31][32][33][34][35][36][37][38][39] On the other hand, gains of chromosomes 8, 19, 21, and 22 have been suggested to be more common in DS-AMKL than in non-DS-AML. 4,10,29,34,38,[40][41][42][43][44][45][46][47] To review in detail the types and frequencies of chromosomal aberrations and to identify novel genetic abnormalities in DS-ALL/ AML, a collaborative study was initiated, collecting data on a total of 404 cytogenetically investigated cases, the largest series of such leukemias to date.…”

Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations

“…A cute leukemia is the most common malignancy in childhood, with an incidence of 4 and 0.7 cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), respectively, per 100,000 children per year (1,2). The outcome for children with ALL and AML has improved significantly over the last two decades, with the overall event-free survival approaching 80% and 50%, respectively (1,3).…”

Trisomy of chromosome 21 in leukemogenesis

“…Three (trisomy) or four (tetrasomy) copies of chromosome 21 is common in childhood acute lymphoblastic leukemia (ALL) [2][3][4]. Children with Down syndrome (DS) who carry trisomy 21 in all their cells have a 20-fold increased risk for childhood ALL and 600-fold risk for acute megakaryocytic leukemia (AMKL) [5].…”