Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogénétique hématologique

Abstract

Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.

AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features

“…44,45 With respect to the gender distribution, female patients represented 69% in our series (9/13 patients) which is supporting data from a previous study where 67% of cases were women. 9 We further could confirm the poor prognosis reported previously, 34,35,[44][45][46] as patients from our series demonstrated a median survival of 4.7 months only. For some part this negative outcome might be explained by the high incidence of t-AML cases in cases of t(8;16) with 54% in our cohort.…”

“…As has been previously reported, 9 all cases examined in our series expressed the myeloid markers MPO, CD33, CD13, CD65 and CD15, but lacked the expression of the progenitor cell markers CD34, CD117 and CD133 (Supplementary Table 2). Furthermore, these cases displayed an expression pattern of the monocytic antigens CD14, CD64, CD11b as well as a coexpression of CD56 and CD4.…”

“…We were able to add 13 new cases to the so far less than 100 reported cases in the Mitelman database (http://cgap.nci.nih.gov/Chromosomes/ Mitelman). 9 Also in our series of AML, the t(8;16) was observed to be very rare, that is, 0.2% of all cases in this study, compared to 0.4% according to Mitelman et al, 43 but its incidence in therapy-related AML was confirmed to be significantly higher, that is, 1.6% in this study. This is in line with data that described for many therapy-induced cases of the t(8;16) subtype the association to previous therapy with alkylating drugs in combination with topoisomerase-II-inhibitors, for example, anthracyclines or epipodophyllotoxins.…”

“…This rare translocation with less than 100 cases described so far, 9 is characterized by disruption and fusion of MYST3 (alias MOZ) and CREBBP (alias CBP) genes. MYST3 is localized on 8p11 and encodes the monocytic leukemia zinc finger protein, a histone acetyltransferase of the MYST family that modulates gene transcription through activation of the AML1 transcription factor complex.…”

Interactive diagnostics in the indication to allogeneic SCT in AML

“…90 So far, survival of a few months only was reported in most cases of MYST-rearranged AML, 87 and none of four patients reported by Quesnel et al 91 achieved CR after standard chemotherapy. Gervais et al 92 reported a mortality rate of 50% in the so far largest study of 30 cases with MYST3/8p11 rearrangements. Successful allo-SCT was reported in one case by Demuynck et al 93 Although the rare occurrence of the translocation has to be seen, there seems to be a clear indication to allo-SCT in the t(8;16).…”