Golay J, Facchinetti V, Ying G, Introna M
Department of Immunology and Cellular Biology, Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
Leuk Lymphoma. 1997 Jul;26(3-4):271-9. doi: 10.3109/10428199709051776.
The myb family of transcription factors has been strongly implicated in the regulation of cell growth and differentiation in the haematopoietic system. The v-myb oncogene, carried by avian defective retroviruses, causes leukaemias in the chicken and transforms haematopoietic cells in vitro. Its normal cellular equivalent c-myb, has been shown to promote the proliferation and block the differentiation of haematopoietic cells in several experimental models and is required for fetal haematopoiesis. Two other members of the family have been cloned more recently, A-myb and B-myb, which show sequence homology with c-myb in several domains, of which the DNA binding domain as well as other regulatory domains. Both have been shown to be transcription factors. B-myb is also involved in the control of proliferation and differentiation, but, unlike c-myb, it is expressed in many cell types. The third member of the family, A-myb, shows the most restricted pattern of expression, suggesting a very specific role for this transcription factor. A-myb is expressed in a subpopulation of normal B lymphocytes activated in vivo and localised in the germinal center of peripheral lymphoid organs and is not detected at significant levels in all other mature or immature haematopoietic populations studied, including bone marrow cells, T lymphocytes, granulocytes, monocytes, either at rest or after in vitro activation. These studies indicate that A-myb plays a role during a narrow window of normal B cell differentiation. A-myb expression has also been studied in a wide range of neoplastic B cells, representing the whole spectrum of B cell differentiation. A-myb is strongly expressed in Burkitt's lymphomas (BL) and slg+ B-acute lymphoblastic leukaemias (B-ALL) and not in all other leukaemias/lymphomas tested, with the exception of a subset of CLL (about 25% of cases). It is intriguing that the A-myb genome has been localised relatively close to the c-myc gene on chromosome 8, suggesting that the c-myc translocation in BL and B-ALL may affect A-myb transcription. Studies are in progress to investigate the functional relationship between A-myb and c-myc, particularly in the context of BL cells and to determine whether A-myb is deregulated in these cells.
转录因子的myb家族与造血系统中细胞的生长和分化调控密切相关。禽源缺陷逆转录病毒携带的v-myb癌基因可引发鸡的白血病，并在体外使造血细胞发生转化。其正常的细胞同源物c-myb已被证明在多个实验模型中可促进造血细胞的增殖并阻止其分化，且对胎儿造血作用至关重要。该家族的另外两个成员A-myb和B-myb是最近克隆出来的，它们在几个结构域中与c-myb具有序列同源性，包括DNA结合结构域以及其他调控结构域。二者均已被证明是转录因子。B-myb也参与增殖和分化的调控，但与c-myb不同的是，它在多种细胞类型中均有表达。该家族的第三个成员A-myb的表达模式最为受限，提示这种转录因子具有非常特殊的作用。A-myb在体内被激活的正常B淋巴细胞亚群中表达，定位于外周淋巴器官的生发中心，而在所有其他研究的成熟或未成熟造血细胞群体（包括骨髓细胞、T淋巴细胞、粒细胞、单核细胞，无论处于静止状态还是体外激活后）中均未检测到显著水平的表达。这些研究表明，A-myb在正常B细胞分化的一个狭窄窗口期发挥作用。A-myb的表达也在广泛的肿瘤性B细胞中进行了研究，这些B细胞代表了B细胞分化的整个谱系。A-myb在伯基特淋巴瘤（BL）和表面免疫球蛋白阳性的B急性淋巴细胞白血病（B-ALL）中强烈表达，而在所有其他检测的白血病/淋巴瘤中均不表达，慢性淋巴细胞白血病（CLL）的一个子集（约25%的病例）除外。有趣的是，A-myb基因座相对定位于8号染色体上的c-myc基因附近，提示BL和B-ALL中的c-myc易位可能影响A-myb转录。目前正在进行研究以探讨A-myb与c-myc之间的功能关系，特别是在BL细胞的背景下，并确定A-myb在这些细胞中是否失调。
