Summary. We studied the expression of HoxA9 and Meis1 by reverse transcriptase-polymerase chain reaction analysis in leukaemic cells from cases of infant acute lymphoblastic leukaemia (ALL, n ¼ 27) and childhood ALL (n ¼ 29). These two genes were co-expressed significantly more frequently in infant ALL than in childhood ALL (19/27 vs 0/29 cases, P < 0AE001) and were highly associated with MLL gene rearrangement in infant ALL cases (P < 0AE001).These findings indicate that the HoxA9 and Meis1 genes are closely associated with MLL gene rearrangement in the development of infant ALL, which represents a distinct entity of childhood ALL.
Summary. The Ikaros (Ik) gene family, which includes Ik, Aiolos (Ai), and Helios (He), is a primary regulator of lymphocyte differentiation, and is involved in the development of acute lymphoblastic leukaemia (ALL). We analysed the expression of the Ik gene family isoforms in 97 ALL cases, consisting of 64 childhood and 33 infant ALL cases, using reverse transcription-polymerase chain reaction (RT-PCR). Expression of Ik was detected in all cases, 87 of which expressed either Ik1 or Ik2, or both, five of which expressed Ik1/Ik2 and Ik6, and another five of which expressed only Ik6. Therefore, the dominant negative isoform of Ik6 was expressed in 10 of the 38 cases of childhood precursor B ALL, but was absent in other types of childhood ALL (26AE3%, v 2 -test, P ¼ 0AE0001). In terms of Aiolos and Helios expression, 49 (65AE3%) out of the 75 and 40 (50%) out of the 80 ALL cases tested showed non-spliced Ai1 and He1 respectively. Only one case of T lineage ALL expressed a small-sized isoform of Helios (designated as He6). It was also found that the expression of Ai1 and He1 was low in Ik6-positive patients (Fisher's exact test; Ai1 P ¼ 0AE005, Hel P ¼ 0AE035).Keywords: Ikaros, Aiolos, Helios, transcription factor, acute lymphoblastic leukaemia.Ikaros, a member of the Kruppel family of zinc finger DNA-binding proteins, plays a critical role in lymphoid cell ontogeny and differentiation (Georgopoulos et al, 1992(Georgopoulos et al, , 1994. Alternative splicing of the Ikaros gene results in the generation of eight isoforms that differ in their DNA binding, dimerization, and nuclear localization potential (Sun et al, 1996). In functional Ikaros proteins, four zinc finger motifs are encoded in the N-terminal region, and at least three of them are needed to bind DNA with high affinity. Ik4-Ik8 possess less than two zinc finger motifs and interfere with functional Ikaros isoforms (Ik1-3) by a dominant negative mechanism (Georgopoulos et al, 1994).According to studies by Georgopoulos and colleagues (Georgopoulos et al, 1992(Georgopoulos et al, , 1994 and Winandy and colleagues (Winandy et al, 1995), lymphocyte development was entirely blocked at its earliest recognizable stage in homozygous mutant mice, having deleted N-terminal zinc finger DNA binding domains in the Ikaros gene. In addition, lymphoblastic leukaemia developed in heterozygous mice 3-6 months after birth. Similarly, Aiolos and Helios, two Ikaros-related genes that dimerize with Ikaros, are expressed predominantly in precursor cells of B and T lineages and are upregulated to their terminal stages of differentiation (Morgan et al, 1997, Wang et al, 1998. Expression of Aiolos was shown to exceed that of Ikaros in mature B cells (Morgan et al, 1997), whereas Helios was primarily expressed in murine T-cell lineage (Hahm et al, 1998). These findings indicate that the Ikaros gene family of proteins is essential to lymphocyte development and that the proteins' altered function may lead lymphoid precursor cells into leukaemia development. In fact, a high level of expr...
We report the case of a 13-year-old girl with diffuse bilateral thalamic astrocytomas. Incoordination was observed at the onset. Cranial computed tomography (CT) showed enlarged thalami, and magnetic resonance imaging (MRI) revealed these lesions to be symmetrically enlarged with high intensity on the T2-weighted image. Owing to these atypical findings in the neuroimaging studies, we had difficulty in making the correct diagnosis of a brain tumor. After the diagnosis of diffuse bilateral thalamic astrocytomas was obtained, we performed hyperfractionated radiotherapy followed by chemotherapy. Radiation therapy was effective for a while, but the girl's condition deteriorated again and she died 8 months after admission. Although diffuse bilateral thalamic astrocytomas are difficult to diagnose because they do not resemble most other neoplasms on neuroimaging studies, pediatricians should keep this entity in mind in order to arrive at a precise and prompt diagnosis.
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