Myelomas arise from an asymptomatic premalignant proliferation of monoclonal plasma cells derived from postgerminal center B cells. In contrast to normal plasma cells, myeloma cells are often immature and may have the appearance of plasmablasts. These cells usually are CD19-CD56^bright, CD38, and syndecan-1, and produce very low amounts of immunoglobulins.

Most patients demonstrate complex karyotype abnormalities with chromosomal gains, deletions, and translocations, some of which are identical to those observed in certain B cell lymphomas. Many numeric and structural abnormalities occur. Primary early chromosomal translocations occur at the immunoglobulin switch region on chromosome 14 (q32.33). This process results in the deregulation of two adjacent genes. Secondary late-onset translocations and gene mutation are implicated in disease progression and include complex karyotypic abnormalities. These genetic abnormalities may prevent the differentiation and apoptosis of myeloma cells, which continue to proliferate and accumulate in the bone marrow. Chromosomal aberrations are of sufficient number to be detected on flow analysis of DNA content, which is aneuploid in about 80% of patients.

Most patients exhibit a slight nuclear DNA excess of 5% to 10%; hypoploidy is observed in only 5% to 10% of patients and is strongly associated with resistance to standard chemotherapy. Deletions of chromosomes 13 and 17 have been observed. The morphologic immaturity, hypodiploidy, and 13q− and 14q+ abnormalities correlate with the resistance to treatment and short survival that are characteristic of aggressive disease.

The somatic mutations of the immunoglobulin genes of myeloma cells indicate that the putative myeloma cell precursors are stimulated by antigens and are memory B cells or migrating plasmablasts.

Myeloma cells proliferate slowly in the marrow (Fig. 1; Table 1). Less than 1% divide at any one time and myeloma cells do not differentiate. The absolute number of these cells correlates with disease activity and predicts the progression of disease in smoldering multiple myeloma. Circulating myeloma cells may disseminate the tumor within the bone marrow and elsewhere.

Fig1. Mechanisms of disease progression in the monoclonal gammopathies. (Adapted from Kyle RA, Rajkumar SV: N Engl J Med 351:1860–1871, 2004.)

Table1. Three Phases of Disease Progression in Multiple Myeloma

Interleukin-6 (IL-6) is essential for the survival and growth of myeloma cells, which express specific receptors for this cytokine. Initially identified as a growth factor for myeloma cells, IL-6 has been shown to promote the survival of myeloma cells by preventing spontaneous or dexamethasone-induced apoptosis. An increased level of IL-6 in the serum of patients with MM can be explained by the overproduction of IL-6 in the marrow. The IL-6 system also has a role in the pathogenesis of bone lesions in MM. IL-6, soluble IL-6 receptor alpha (sIL-6Rα), and interleukin-1 beta (IL-1β) activate osteoclasts in the vicinity of myeloma cells and thus initiate bone resorption. IL-6 may account for MM-associated anemia and for the lack of thrombocytopenia because of its stimulation of megakaryopoiesis.

اخر الاخبار

اخبار العتبة العباسية المقدسة

وفد العتبة العباسية المقدسة يجري جولة في أروقة معرض بغداد الدولي للكتاب

شعبة التوجيه الديني النسوي تطلق برنامجًا قرآنيًّا لزائرات مرقد أبي الفضل العباس (عليه السلام)

جامعة الكفيل تطلق دورة تدريبية عن تقييم الأداء الجامعي لعدد من ملاكاتها

المجمع العلمي يقيم محفلًا قرآنيًا بذكرى ولادة الصادقين (صلوات الله عليهما)

المزيد

الآخبار الصحية

هل يتنبأ الذكاء الاصطناعي بأمراضنا قبل حدوثها؟

وداعا للنظارات.. قطرة عين واحدة قد تغير كل شيء ؟

دراسة تكشف تأثير "تيك توك" وتطبيقات الفيديو على سلوك الأطفال

"أسرار خفية" في الشاي الأخضر.. تغير قواعد الصحة والوزن

المزيد

الآخبار التكنلوجية

أول قطار يعمل بالهيدروجين في أميركا يدخل الخدمة رسميًا

أجهزة أبل القادمة.. "حصن منيع" في عصر الهجمات الرقمية !

روسيا: تطلق قمرين اصطناعيين بواسطة الصاروخ سويوز 2.1

ميزة ثورية.. أبل تدخل عالم قياس ضغط الدم

المزيد

مواضيع ذات صلة

Diagnostic Evaluation of Multiple myeloma

Signs and Symptoms of Multiple myeloma

CANCER

العوامل البيئية المسببة للسرطان

الأورام الصماوية للبنكرياس

متلازمة الأورام الغدية الصماوية المتعددة Multiple Endocrine Neoplasia (MEN) Syndrome

خصائص الخلايا السرطانية

Testicular germ cell tumours

Prostate carcinoma

Renal cell carcinoma

المسببات الكيميائية للسرطان chemical causes of cancer

الوراثة والسرطان Genes associated with cancer