Acute myelomonocytic leukemia with abnormal eosinophils and inv(16) or t(16;16) has a favorable prognosis

Abstract

Inv(16)(p13q22) and t(16;16)(p13;q22) are recurring chromosomal rearrangements which juxtapose the metallothionein gene cluster at 16q22 with other DNA sequences from 16p13. We have studied 20 men and 13 women who had acute nonlymphocytic leukemia; 27 patients had an inv(16) and six patients had a t(16;16). Eight patients also had trisomy 22, and four had trisomy 8. All but two patients had the unique morphologic features of acute myelomonocytic leukemia with abnormal eosinophils (M4Eo). In one patient with M4 leukemia, abnormal eosinophils were not observed in the marrow. A second patient had acute monocytic leukemia, plus abnormal eosinophils. Eosinophils constituted 1% to 46% (median, 6%) of the bone marrow cells, and in all but a single patient, the eosinophils exhibited distinctly abnormal morphology. Twenty-five patients have had a complete remission (78% of treated patients). Nine patients have remained in remission longer than 24 months. No patient had symptoms of central nervous system (CNS) disease at diagnosis, and none had CNS leukemic mass lesions at any time. Treatment with high-dose cytarabine may have provided prophylactic CNS therapy. Four additional patients with chromosomal rearrangements involving a breakpoint at 16q22 but not at 16p13 have had different morphological features and different clinical courses. Thus, the juxtaposition of genes at 16p13 and 16q22, which occurs both in the inv(16) and the t(16;16), results in a specific subset of acute nonlymphocytic leukemia that has a favorable prognosis.

Chromosome 16 abnormalities associated with myeloid malignancies

“…Arthur and Bloomfield (1983) and subsequently Le Beau et al (1983) observed that this group of patients appeared to have an improved survival compared with ANLL patients as a whole. This finding has been supported by data from other groups (Holmes et al, 1985;Larson et al, 1986) 0 1991 WILEY-LISS, INC.…”

“…T h e incidence of 8% in our series is comparable with that of ANLL in general. Larson et al (1986) also failed to observe a marked increase in the incidence of this complication. However, preparatory chemotherapy and/or radiotherapy regimens for autologous and allogeneic bone marrow transplants received by 9 of our patients may have affected the incidence of CNS relapse in these patients.…”

“…Abnormalities additional to those involving 16 have frequently been described in the literature. Larson et al (1986) described 6 patients with trisomy 22, 4 patients with trisomy 8, and 3 patients with del(7q) in addition to chromosome 16 abnormalities, and Holmes et al (1985) also reported trisomy 8 and trisomy 22 as frequent additions. Two of our patients had trisomy 22 and a further 2 had trisomy 9.…”

Inversion‐associated translocations in acute myelomonocytic leukemia with eosinophilia

“…Whether del(16) results in similar molecular rearrangements is presently not known. Besides inv(l6) and del( 16), variant translocations involving chromosome 16 (Hogge et al, 1984;Larson et al, 1986;Bernard et al, 1989) and another chromosome (1, 3, 5, and 8) have been reported in M4EO (de la Chapelle and Lahtinen, 1983;Yip et al, 1991;Bernard e t al., 1989;Thompson et al, 1991;Bhambhani et al, 1986;Berger and Dombret, 1992). Most of the variant translocations, t( 16; 16) escepted, involve the band 16q22, but not 1 6~1 3 .…”

Underestimation of inversion (16) in acute myeloid leukaemia using standard cytogenetics as compared with polymerase chain reaction: results of a prospective investigation

“…Recent data from the Cancer and Leukemia Group B indicate that patients with t(8;21) may have an excellent prognosis after high-dose cytosin-arabinoside therapy and may therefore not be in need of allogeneic bone marrow transplantation as intensive post-induction therapy (Bloomfield et al, 1994). Many authors have also included patients with inv(16) in this favourable subgroup of AML (Larson et al, 1986;Marlton et al, 1995). From a molecular point of view, this is intriguing, since in both lesions the identical transcription factor complex (CBF-a, CBF-b) is targeted by the translocation t(8;21) as well as inv(16) Castilla et al, 1996;Meyers et al, 1995).…”