inv(8)(p11.2q13) found in a patient with chronic myelomonocytic leukemia that progressed to acute myeloid leukemia

Jennifer JS Laffin, Sara J Morrison-Delap, Wayne A Bottner, Eric B Johnson, Patricia Howard-Peebles, Kate J Thompson, Gordana Raca, Karen D Montgomery, Daniel F Kurtycz Affiliation

University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, University of Wisconsin Cytogenetic Services, Wisconsin State Laboratory of Hygiene, Madison, WI, USA (JJSL); University of Wisconsin Cytogenetic Services, Wisconsin State Laboratory of Hygiene, Madison, WI, USA (SJMD) (EBJ) (KJT); Gundersen Lutheran Medical Center, La Crosse, WI, USA (WAB); University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pathology and Laboratory Medicine, University of Wisconsin Cytogenetic Services, Wisconsin State Laboratory of Hygiene, Madison, WI, USA (PHP) (GR) (KDM) (DFK)

Previous history

Preleukaemia

Malignant disease

Inborn condition

Main items

67 year old man with normal CBC until 02.23.1993, when first noted to have monocytosis (wbc 6900; mono 17%; Absolute Mono Count (AMC) 1173/mm3), mild anemia (Hgb 13.4/ nl 13.6-16.7) and thrombocytopenia (121,000/nl 150-400,000). Otherwise clinically well. No significant other medical history. CMML by marrow biopsy 12/2001 (WBC 15,300; Hg 13.0; plt 65,000; AMC 3060/mm3). Initial cytogenetic analysis was normal, 46,XY. No treatment for 5 years because of stable counts and no symptoms. He presented with fatigue and purpura December 2006 (see description below)

Clinics case report

Age

67 yrs

Sex

Liver

Spleen

Lymph nodes

Cns involv

Blood data

Wbc

30.5

13.5

Platelets

Blasts

Bone marrow

AML, M4; 80% monocytoid blasts.

Cyto path

Cytology

Immunophenotype

Negative for: CD34, CD2, CD3, CD19, CD20, TdT, cyto CD3, CD7

Rearranged ig tcr

not done

Pathology

AML, M4

Electron microscopy

not done

Precise diagnosis

AML, M4

Survival data

Date diagnosis

12-2006

Treatment

Ara-C/Daunorubicin

Complete remission

+; marrow still recovering as of 02/09/07 w/ WBC 1900; ANC 670; Hg 10.0; plt 63,000; Abs Mono Count 228

Relapse

Phenotype relapse

normal karyotype 46,XY. The patient died shortly after the last cytogenetic analysis due to disease relapse.

Status

Date last follow

02-2007

Survival

Karyotype

Sample

Bone Marrow

Culture time

Overnight and 24

Banding

G-banding; 450 band level

Results

46,XY,inv(8)(p11.2q13)[6]/46,XY[14]

Images

Partial metaphases and partial karyotypes showing the inv(8)(p11q13)

Comments section

Comments

A review of the literature revealed six reports of inv(8)(p11q13) associated with AML M4 or M5 all involving female patients ages 10 months, 15, 19, 21, 29, and 56 years old (References 1-6, 8-9). This is the first report of inv(8)(p11.2q13) associated with AML M4 in a male patient and older than 56 years. The inversion causes the fusion of the MOZ gene at 8p11.2 with TIF2 at 8q13. Deguchi et al described the requirement for C2HC nucleosome recognition of MOZ and the CBP recruitment activity of TIF2 for transformation leading to leukemogenesis. The propensity of affected females requires further investigation, but may just be a bias in the literature (Reference 7).

Article Bibliography

Pubmed ID	Last Year	Title	Authors
9376594	1997	Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.	Aguiar RC et al
9558366	1998	A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia.	Carapeti M et al
9504640	1998	Two cases of inv(8)(p11q13) in AML with erythrophagocytosis: a new cytogenetic variant.	Coulthard S et al
9731070	1998	Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2.	Liang J et al
11342350	2000	Acute myeloid leukemia with inv(8)(p11q13).	Panagopoulos I et al
12010678	2002	A further case of acute myeloid leukaemia with inv(8)(p11q13) and MOZ-TIF2 fusion.	Billio A et al
12676584	2003	MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP.	Deguchi K et al
12619166	2003	Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11).	Imamura T et al
12964013	2003	A further case of acute myelomonocytic leukemia with inv(8) chromosomal rearrangement and MOZ-NCOA2 gene fusion.	Murati A et al

Citation

Jennifer JS Laffin, Sara J Morrison-Delap, Wayne A Bottner, Eric B Johnson, Patricia Howard-Peebles, Kate J Thompson, Gordana Raca, Karen D Montgomery, Daniel F Kurtycz

inv(8)(p11.2q13) found in a patient with chronic myelomonocytic leukemia that progressed to acute myeloid leukemia

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: http://atlasgeneticsoncology.org/case-report/208825/favicon/case-report-explorer/gene-fusions-explorer/