Biologic and cytogenetic characteristics of leukemia in infants

Abstract

Clinical features, leukemic cell characterization, chromosomal findings, and treatment outcome were analyzed in a retrospective study of 30 cases with acute leukemia of infancy, 24 infants with acute lymphoblastic leukemia (ALL), and six cases with acute nonlymphoblastic leukemia (ANLL). Extensive bulky disease with organomegaly, central nervous system (CNS), and skin involvement were prominent features at diagnosis with a higher frequency in ANLL as compared to ALL. Four of six ANLL patients were classified as monocytic or myelomonocytic. In the ALL group nine of 24 (36%) were non-L1 morphology and six of 17 (33%) were common ALL antigen (CALLA) negative, the majority of them (five of six) were included in the non-L1 group. Immunophenotyping revealed four cases with early B-cell (three patients: Ia+B4+, and one patient: Ia+) and two cases with T-cell. Mixed lineage leukemia was found in five infants. Heavy chain immunoglobulin gene rearrangement was present in six cases tested, two CALLA+, two with Ia+B4+, and two were undifferentiated mixed lineage leukemia. Chromosomal aberrations were detected in ten of 18 patients, mostly in ANLL and CALLA negative ALL. Translocations were detected in six patients, involving 4q21-23 and 11q23 in three and two cases, respectively. The probability of five-year DFS were 27% for the whole group. The worst prognosis was observed in infants younger than 6 months of age, in whom the leukemia cell characteristics was compatible with stem cell: ANLL, very early pre-B, or undifferentiated mixed type. The chromosomal aberrations found in all cases included translocation with the seemingly nonrandom breakpoints at 4q21 and 11q23, and breakpoints that corresponded to known fragile sites. This finding may be suggestive of an underlying genetic predisposition associated with the poor prognosis of leukemia of infancy.

Infant Acute Lymphoblastic Leukemia: A 20-Year Children's Hospital Experience

“…Compared with older children, infants with ALL present more often with a white blood count >50,000/uL (47% vs.18%), hepatomegaly (18% vs. 6%), and splenomegaly (23% vs. 8%) [5]. Infants are more likely to have multiorgan involvement, and they have a greater frequency of CNS disease (20% vs. 4.1%) [5][6][7]. Our 66.7% CNS involvement, 75% extramedullary involvement, and 62.5% with WBC > 50,000/uL may reflect either this more extensive disease in infants or perhaps a delay in presentation of our patients.…”

“…Lymphoblasts in infants are more likely to be CD19-positive and cALLA/CD10 negative precursor B-lineage (pro-B) than cells in older children [1,6]. Infant lymphoblasts often co-express myeloid-associated antigens, such as CD15 and CDw65 [1], consistent with early immature cells.…”

Childhood acute lymphoblastic leukemia: update on prognostic factors

“…In general, MLL-rearranged ALL has a distinctive pro-B immunophenotype characterized by CD-10 negativity [28]. MLL-rearranged ALL is considered a biologically unique leukemia subtype that can be distinguished from other leukemia by gene expression profiling [29].…”

Deletion of chromosome 11 and of 14q sequences in neuroblastoma

“…Chromosome 11 has been implicated in a number of human tumors (Fearon et al, 1985;Koufos et al, 1985;Ali et al, 1987Ali et al, , 1989Larrson et al, 1988;Stark et al, 1989;Ehlen and Dubeau, 1990;Jin et al, 1990;Srivatsan et al, 1991) and cytogenetic rearrangement involving the long arm of chromosome 11 [inv(l l)(pter+q21: :q23+qZ1: :qZ3--+ qter)] has been reported in a familial neuroblastoma (Hecht and McCaw, 1981). Therefore, in the present investigation, we analyzed 45 primary tumors to determine the frequency of deletions of chromosome 1 1 and the relationship to genomic Analysis of tumors with 14q-specific probes showed deletion of 14q amplification of MYCN, the deletion of 14q sequences, and clinical parameters.…”