Double Supernumerary Isochromosome 9p in Myeloproliferative Syndrome

Joe-Jie Hoo, Sharon O'Brien, and Iris Samuel

ABSTRACT: The presence of supernumerary isochromosume 9p in duplicate in about 50% of bone mar row cells of an elderly female patient with myeloproliferative syndrome is reported.

INTRODUCTION

Only few cases of const i tut ional supernumerary i sochromosome 9p [i(9p)] are known in the l i terature [1]. Much rarer is the report of an i(9p) as an acquired aberrant chromosome in mal ignant cells [2]. We report here the presence of i(9p) in bone marrow cells of a pat ient with myeloprol i ferat ive syndrome (MDS).

CASE REPORT

A 76-year-old female pat ient was admit ted to hospi ta l for a left-sided lens insert ion fol lowing a successful cataract extract ion 6 years earlier. Her past medical history revealed a mi ld hyper tens ion and anemia, which was treated with iron pills. Her laboratory investigations at this admiss ion showed normal serum electrolytes, glu- cose, cholesterol, a lbumin, bi l i rubin, creatine kinase, and aspartate aminotrans- ferase. However, her creatinine, urea, alkal ine phosphatase, and lactate dehydroge° nase were sl ightly higher than the respect ive upper normal limit. The complete blood count revealed a white blood cell count of 2 0 , 4 0 0 / m m 3, red blood cell count 3.8 mi l l ion /mm 3 and platelet count of 813,000/mm3; hemoglobin 11.2/g/dl. The red cell indices, pro thrombin time, part ial thromboplas t in time, and the bleeding t ime were wi thin normal ranges.

Bone marrow biopsy revealed small and fragmented bone trabeculae. The mar- row spaces were 95% cellular. The megakaryocytes were increased in number and in focal areas were in clusters. Two lympho id aggregates were identified. The M:E ratio was 8:1. The myelo id series showed both immature and mature forms. The erythropoesis appeared normal. The iron stores were increased. The ret icular fibers were mi ld ly increased. The above findings were considered to be consistent with a myeloprol i ferat ive disorder.

Direct and 24-hour culture chromosome preparat ions from a bone marrow spec- imen were performed. Fifty-five metaphase cells were examined using conven- tional, Q- and G-banding staining procedures. About 50% of the cells showed a

From the Department of Pediatrics, University of Illinois at Chicago (J.J.H., I.S.), and the Department of Histopathology, Foothills Hospital, Calgary/Canada (S.O.).

Address requests for reprints to J.J. Hao, Dept. of Pediatrics, University of Illinois at Chi- cago, 840 S. Woad St., Chicago, IL 60612.

Received March 30, 1987; accepted May 18, 1987.

3 1 9

© 1987 Elsevier Science Publishing Co., Inc. Cancer Genet Cytogenet 29:319-321(1987) 52 Vanderbilt Ave., New York, NY 10017 0165-4608/87/$03.50

320 J-J Hoo, S. O'Brien and I. Samuel

9 i(gp)

+i|++ Z

Figure 1 and i(9p).

Partial karyotypes of two G-banded cells showing the normal chromosomes #9

modal number of 48 chromosomes with the presence of two supernumerary marker chromosomes, which were metacentric and identical in size. Their banding pattern appeared to be compatible with an i(9p) (Fig. 1). The remaining 50% of the cells showed a normal female karyotype of 46,XX.

DISCUSSION

Various isochromosomes had been reported in various hematopoetic malignancies and solid tumors [2]. Some were considered to be a specific chromosomal marker for a particular malignancy, such as i(12p) in malignant testicular tumors [3]. Others were considered to be an indicator of a certain stage of the disease, such as the appearance of i(17q) in chronic myelocytic leukemia as an indicator that the disease is transforming into acute blastic crisis [4]. But in most other cases, the appearance of isochromosomes remains unexplained.

References to an acquired i(9p) is rather scant. Martin et al. [5] and Reichmann et al. [6] described an i(9p) in colon cancer and Augustus and Gebhart [7] recently found an i(9p) in metastatic effusion cells of a squamous cell carcinoma of the cervix uteri. The present report described supernumerary i(9p) in bone marrow cells.

One might speculate that the presence of an isochromosome is somehow asso- ciated with the proliferation of a certain oncogene on that isochromosome. But, to our knowledge, there has been no assignment of a protooncogene to 9p. If, however, the presence of isochromosome were speculated as being associated with the pro- liferation of certain defence mechanism, then the location of alpha interferon gene on 9p and its proliferation with the presence of double supernumerary i(9p) might be seen as supporting this speculation.

i(9p) in MDS 3 2 1

REFERENCES

1. Moedjono SJ, Crandall BF, Sparkes RS (1980): Tetrasomy 9p: Confirmation by enzyme anal- ysis. J Med Genet 17:227-242.

2. Mitelman F (1983): Catalogue of chromosome aberrations in cancer. Cytogenet Cell Genet 36:1-516.

3. Delozier-Blanchet CD, Engel E, Walt H (1985): Isochromosome 12p in malignant testicular tumors. Cancer Genet Cytogenet 15:375-376.

4. Goh KO, Rubins J (1985): Isochromosome 17q in Ph-negative chronic myelocytic leukemia. Cancer Genet Cytogenet 14:323-330.

5. Martin P, Levin B, Golomb HM, Riddell RH (1979}: Chromosome analysis of primary large bowel tumors: A new method for improving the yield of analyzable metaphases. Cancer 44:1656-1662.

6. Reichmann A, Martin P, Levin B (1981): Chromosomal banding patterns in human large bowel cancer. Int J Cancer 28:431-440.

7. Augustus M, Gebhart E (1986): Isochromosomes in human carcinomas. Abstracts. 7th Inter- national Congress of Human Genetics, Berlin, September 22-26. 1986, p. 551-552.