SHORT COMMUNICATION

Trisomy of Chromosome 22 in Acute Myelomonocytic Leukemia

Menco M. G. Niemeyer, Hans L. Haak, Els Augustinus, Jos6 I. den Nijs-van Weert, and Christiaan H. W. Leeksma

ABSTRACT: A patient with acute myelomonocytic leukemia type M4, with a trisomy 22 as the only chromosomal abnormality is reported. All six previously published cases with this anomaly had acute myeloid leukemia. The subtype was AMMoL in five patients, and the subtype of the sixth one was not indicated.

I N T R O D U C T I O N

During recent years a number of acquired clonal chromosomal abnormali t ies have been reported, correlating with part icular subtypes of acute non lymphocyt ic leu- kemia (ANLL) and characterist ic morphologic and cl inical features [1-5]. We have observed a patient with acute myelomonocyt ic leukemia (AMMoL) who had tri- somy of chromosome #22 as the only abnormali ty.

C A S E R E P O R T

A 73 year old woman was admit ted because of severe dyspnea on exertion. Her past medical history was unremarkable. Physical examinat ion revealed pal lor wi th ab- sence of organomegaly or lymphadenopa thy , and no leukemic infiltrates in the skin. The concentrat ion of hemoglobin was 5.4 mmol/1, platelets 35 x 10 9, WBC count 97 x 109/1 with 14% blast cells, 4% segmented neutrophits , 15% lymphocytes , and 67% monocytes and monocyto id myelocytes.

Bone marrow smears revealed a hypercel lu lar bone marrow with severe de- creased erythropoiesis , few megakaryocytes, and about 80% blast cells, monocytes, promonocytes , and monocyto id myelocytes (Fig. 1). Cytochemical studies con- firmed the myelomonocyt ic nature of the leukemia suggested by the May-Gr i inwa ld stain. In the Sudan black B stain, a coarse localized pattern was found in about 40% of the cells and a scattered granular pat tern in about 60%. In a dual esterase stain, a large fraction of the cells showed a strong reaction for naphthol acetate esterase blocked by NaF, and another fraction of cells with a strong chloroacetate esterase reaction. The per iodic ac id-Schi f f stain showed a diffuse finely granular pattern. Therefore, a diagnosis of AMMoL M4 was made.

Combined chemotherapy (teniposide, cytosine arabinoside, vinblast ine, and

From the Department of Hematology, Municipal Hospital Leyenburg, The Hague, The Netherlands.

Address requests for reprints to Dr. C. H. W. Leeksma, Department of Hematology, Munic- ipal Hospital Leyenburg, Leyweg 275, 2545 CH The Hague, The Netherlands.

Received May 16, 1985; accepted August 12, 1985.

371

© 1986 Elsevier Science Publishing Co., Inc. Cancer Genet Cytogenet 20:371-374 (1986} 52 Vanderbilt Ave., New York, NY 10017 0165-4608/86/$03.50

372 M . M . G . N iemeye r et al.

F igure 1 Bone marrow histology. Note numerous monocytoid cells and absence of eryth- ropoiesis. Methyl-methacrylate, Gallamine-Giemsa x 600. Courtesy of J. te Velde.

p redn i sone) was admin i s t e red , but the response was poor and the pa t ient had to be m a i n t a i n e d on b lood t ransfus ions . She d ied after 4.5 m o n t h s of s ep t i cemic and

hemor rhag i c compl i ca t ions .

CHROMOSOME STUDY

C h r o m o s o m e s l ides of pe r iphera l b lood cel ls were p repa red by a hot band ing m e t h o d recen t ly r epor t ed [6], and s ta ined w i t h Giemsa. A 24-hour u n s t i m u l a t e d cu l ture showed : 4 6 , X X = 7, 4 7 , X X , + 2 2 = 8 (Fig, 2). A 96-hour cu l ture w i t h PHA

showed : 4 6 , X X = 12.

DISCUSSION

Tr i somy 22 (Fig. 2) as the on ly karyo typ ic a n o m a l y is of rare occur rence ; however , it has been desc r ibed more f r equen t ly in c o n j u n c t i o n w i t h o ther c h r o m o s o m a l ab- normal i t ies . Unt i l now, as far as we cou ld ascertain, on ly six cases w i t h t r i somy 22

Tab le 1 Pat ients w i t h t r i somy 22

FAB Survival Karyotype Age (yr) diagnosis Remission (mo) Ref.

47,XX, + 22 19 U yes U [7] 46,XY/47,XY, + 22 child M4 yes 18 [8] 47,XY, + 22 22 M4 yes U [9] 46,XX/47,XX, + 22 27 M4 no 1 [101 46,XY/47,XY, + 22 10 M4 yes 18 [11] 46,XY/47,XY, + 22 58 M4 yes 22 [12] 4B,XX/47,XX, + 22 73 M4 no 5 [Present case]

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as the sole abnormal i ty have been repor ted [7-12]. These were all cases of ANLL. In one case, the sub type was not repor ted; the o ther five cases were all AMMoL (Table 1). The f inding in these pat ients w i th t r i somy 22 suggest an associa t ion wi th AMMoL, no re la t ion wi th age and sex, and no h is tory of m u t a g e n i c exposure . Al- t hough no r emis s ion was ob ta ined in our case, o ther s tudies have s h o w n a substan- tial r emi s s ion rate. The dura t ion of these r emiss ions appears to be about average for this disorder .

REFERENCES

1. Rowley JD (1973): Identification of a translocation with quinacrine fluorescence in a pa- tient with acute leukemia. Ann Genet 16:109.

2. Rowley JD, Colomb HM, Dougherty C (1977): 15/17 Translocation, a consistant chromo- somal change in acute promyelocytic leukemia. Lancet i:549-550.

3. Berger R, Bergheim A, Siguax F, Daniel MFH, Valensi F, Flandrin G (1982): Acute mono- cytic leukemia chromosome studies. Leuk Res 6:17-26.

4. Hagemeyer A, H~ihlen K, Sizoo W, Abels J (1982): Translocation (9;11) (p21;q23) in three cases of acute monoblastic leukemia. Cancer Genet Cytogenet 5:95-105.

5. Lebeau MM Larson RA, Bitter MA, Vardiman JW, Golomb HM, Rowley JD (1983): Asso- ciation of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia: A unique cytogenetic-clinic-pathological association. N Engl J Med 309:630-636.

6. Nijs JI den, Gonggrijp HS, Augustinus E, Leeksma CHW (1985): A simple G-banding method for leukemic methaphases. Cancer Genet Cytogenet 15:373-374.

7. Oshimura MS, Hayata J, Kakati S, Sandberg AA (1976): Chromosomes and causation of human cancer and leukemia. XVII Banding studies in acute myeloblastic leukemia (AML). Cancer 38:748-761.

8. Zueler WW, Inoue S, Thompson RI, Ottenbreit MJ (1976): Long-term cytogenetic studies in acute leukemia of children; The nature of relapse. Am J Haematol 1:143-190.

9. Shiloh Y, Naparstek E, Cohen MM (1979): Cytogenetic investigation of leukemic and pre- leukemic disorders. Israel J Med Sci 15:500-506.

10. Mitelman F, Nilsson PG, Brandt L, Alimena G, Gastaldi R, Dallapiccola B (1981): Chro- mosome pattern, occupation, and clinical features in patients with acute nonlymphocytic leukemia. Cancer Genet Cytogenet 4:197-214.

11. Bernard P, Reiffers J, Lacombe F, Dachary D, Bavid B, Boisseau MR, Broustet A (1982): Prognostic value of age and bone marrow karyotype in 78 adults with myelogenous leu- kemia. Cancer Genet Cytogenet 7:153-163.

12. Brodeur GM, Williams DL, Kalwinsky DK, Williams KJ, Dahl GV (1983): Cytogenetic fea- tures of acute nonlymphoblastic leukemia in 78 children and adolescents. Cancer Genet Cytogenet 8:93-105.

13. McCarthy DM, Rassool FV, Goldman JM, Graham S, Birnie GD (1984): Genomic alterations involving the c-myc proto-oncogene locus during the evolution of a case of chronic gran- ulocytic leukemia. Lancet ii:1362-1365.

ADDENDUM

After c o m p l e t i o n of this c o m m u n i c a t i o n we b e c a m e aware of a repor t on abnormal - i t ies of c h r o m o s o m e #22 . In this repor t three cases wi th an extra c h r o m o s o m e #22 , all three wi th M4 morpho logy , are m e n t i o n e d (Four th In te rna t iona l W o r k s h o p on C h r o m o s o m e s in Leukemia , 1982 (1984): Abnorma l i t i e s of c h r o m o s o m e 22. Cancer Genet Cytogent 11:316-318).