Two cases of inv(8)(p11q13) in AML with erythrophagocytosis: a new cytogenetic variant

Abstract

Summary.We describe two patients with acute myeloid leukaemia (AML) associated with erythrophagocytosis and a pericentric inversion of chromosome 8, inv(8)(p11q13). The haematological features were indistinguishable from those of patients with the t(8;16) syndrome and its variants. Our observations emphasize the importance of the breakpoint at 8p11 and the possible involvement of the MOZ gene in all these cases.Keywords: acute myeloid leukaemia, M4/M5 subtypes, erythrophagocytosis, t(8;16), cytogenetic variant.The translocation t(8;16)(p11;p13) is a rare cytogenetic abnormality which almost always accompanies a diagnosis of acute myelomonocytic leukaemia (AML FAB-M4) or acute monocytic leukaemia (AML FAB-M5) with erythrophagocytosis by the leukaemic blasts. Several variants, always with the 8p11 breakpoint, have been reported, most notably t(8;19) and t(8;22) (Lai et al, 1992;Stark et al, 1995). A further variant is presented here, seen in two patients with the clinical features of this rare AML subtype. CASE REPORTS Patient 1A 15-year-old Indian girl was referred from another hospital for further investigation and treatment of acute myeloid leukaemia. On examination she was not distressed. There were no ecchymoses, petechiae, peripheral lymphadenopathy or abdominal organomegaly. She was febrile, 38ЊC, with no evidence of any infective focus. Mild gum hyperplasia was present and there was an acneiform rash on the face and back. Investigation revealed a haemoglobin of 9·8 g/dl (posttransfusion), white cell count of 1·0 × 10 9 /l with a neutrophil count of 0·1 × 10 9 /l and platelets 99 × 10 9 /l. Occasional large blasts were present on the blood film. The prothrombin time was prolonged at 17·8 s (normal 13-15 s); this was later shown to be due to a mild factor VII deficiency. The APTT, thrombin time and fibrinogen were normal. The bone marrow aspirate was hypercellular with 98% blasts. These were large with basophilic cytoplasm, scanty granulation and a low nuclear/cytoplasmic ratio. No Auer rods were seen. Phagocytosis of erythroid and granulocyte precursors was prominent, with many blasts showing single or multiple clear phagosomes (Figs 1a and 1b). Mitotic figures were prominent. The majority of blasts were weakly positive with alpha-naphthyl butyrate esterase (monocytic) and < 5% positive for chloroacetate esterase (granulocytic). The morphological features and immunophenotyping were consistent with a diagnosis of AML, FAB-M5a.Cytogenetic analysis was performed on 10 metaphases from unfractionated bone marrow, cultured using standard methods. Seven showed a pericentric inversion of one chromosome 8, with breakpoints at p11 and q13 (Fig 2a) and the remaining three metaphases had an apparently normal karyotype. Fluorescence in situ hybridization using a whole chromosome paint for 8 was performed to exclude the presence of a cryptic rearrangement involving any of the usual partner chromosomes in the t(8;V). There was no signal visible on any chromosome other than the normal and inverted chromosome 8s.The patient...

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

“…As given in Figure 3d, the discovered signature from HG-U133A/B microarrays was validated using data obtained from an independent cohort of patients analyzed with HG-U133 Plus 2.0 microarrays. A similar clustering was observed for an independent series of 3 cases of AML with t(8;16), repeatedly intercalating with the group of t(11q23)/MLL (n ¼ 10), but being clearly distinct from other AML subtypes with balanced chromosomal aberrations (inv (16), n ¼ 7; t(15;17), n ¼ 15; t(8;21), n ¼ 16).…”

“…However, the question of the relevant leukemogenic fusion is still under debate. 13 Moreover, both genes involved in the translocation t(8;16) are known to be involved in other rare balanced rearrangements in AML, all associated with an adverse prognosis: MYST3 in t(8;19)(p11;q13), 14 t(6;8)(q27;p11), t(8;22)(p11;q13) 15 and inv(8)(p11q13); [16][17][18] CREBBP in t(10;16) (q22;p13) 19 or t(11;16)(q23;p13), 20 respectively.…”

Hemophagocytosis by Leukemic Blasts in T Cell Acute Lymphoblastic Leukemia: An Unusual Finding

“…In addition, honeycomb like vacuoles with phagosomes have also been reported [4]. Two other cases of AML with complex cytogenetic abnormality showing hemophagocytosis have been described by Coulthard et al These patients had inv(8)(p11q13) [5].…”

“…Hemophagocytosis by leukemic blasts is an uncommon phenomenon and has been described in AML [2,4,5], ALL [6,7], chronic myelogenous leukemia (CML) in blast crisis [8] and myelodysplastic syndrome (MDS) [9].…”

“…Patients in whom hemophagocytosis by myeloid blasts has been reported showed complex cytogenetic abnormalities [2, 4, 5,], poor response to therapy [5] and poor prognosis [8]. No reports of hemophagocytosis by T lymphoblasts were found on a detailed literature search.…”