New recurring chromosomal translocations in childhood acute lymphoblastic leukemia

We have recently cloned the human cDNA for a gene, denoted D4, that encodes a protein 67% identical to the bovine rhoGDI protein, a GDP dissociation inhibitor (GDI) for the ras-related rho-subtype proteins. We now present data on the cloning and structural analysis of the murine D4 cDNA and confirm its preferential expression in hematopoietic tissues. The predicted murine and human D4 proteins are almost 90% identical, indicating that D4 and rhoGDI are different genes and that they are probably members of a related family of genes. Functional studies with the human D4 protein demonstrate that D4 has GDI activity against the CDC42Hs and rac I proteins, but binds to these proteins with a significantly weaker affinity than does the rho-subtype GDI. These data suggest that D4, which will in subsequent communications be denoted as GDI.D4, might be a GDI for other known or as yet unidentified ras-like GTP-binding proteins. Alternatively, D4 could have other biochemical functions. During murine embryogenesis, D4 transcripts are detected in yolk-sac cells, where the earliest hematopoietic precursors are found. When these precursors undergo proliferation and differentiation in vitro, a dramatic increase in D4 expression is seen. D4 probably has a significant function during the growth and development of hematopoietic precursors.

Section: Discussionmentioning

confidence: 99%

Identification of a novel protein with GDP dissociation inhibitor activity for the ras‐like proteins CDC42Hs and Rac 1

Adra

Ko²,

Leonard

et al. 1993

“…Abnormalities of 12p associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were also described (Mitelrnan, 1991). Several recurring 1Zp translocations, i. e., t( 12; 13)( p 13; q 14), t( 12; 17) (p 13;qZ l), dic( 12; 17)( pl 1 ; pl 1-p 1 Z), and dic( 7; 12) (pll;p12), have been reported (Raimondi et al, 1586(Raimondi et al, , 1991Mitelman, 1991;Krance et al, 1952), but different bands on 12p were involved in these translocations. Moreover, some 12p deletions show phenotypes similar to those seen in 12p translocations (Raimondi et al, 1986;Mitelman, 1991).…”

mentioning

confidence: 99%

Identification of cytogenetically undetected 12p13 translocations and associated deletions with fluorescence in situ hybridization

Kobayashi

Rowley

1995

We performed fluorescence in situ hybridization (FISH) on bone marrow or peripheral blood cells thought to contain a del(12p) or an unbalanced 12p11-12 translocation from 17 patients who had various hematologic malignant diseases. We used 11 cosmid, phage, and plasmid probes which we had previously ordered on 12p. Cells from three patients with myeloid disorders were shown to have 12p13 translocations that involved chromosome 2 in two of them. Moreover, in all patients, FISH showed that the translocations were associated with proximal interstitial deletions which contributed to the difficulty in identifying these translocations. Our data suggest that some rearrangements of 12p which have been described previously as deletions or unbalanced translocations may, in fact, represent 12p13 translocations accompanied by an interstitial deletion.

“…This is not unexpected; del(7p) is relatively frequent in ALL, and del(7q) is a well-known abnormality in myeloid neoplasms (Johansson et al, 1993). Further support for the association between concomitant 7p and 12p losses and ALL has been provided by Raimondi et al (1991), who described a dic(7;12)(pll;p12) in five ALLs. Similar dicentric chromosomes, but with breakpoints mapping to 7pll and 1 2~1 1 , have been reported in two ALLs by the UKCCG (1992) and by Pui et al (1993).…”

Section: Discussionmentioning

confidence: 86%

Fluorescence in situ hybridization analysis of whole‐arm 7;12 translocations in hematologic malignancies

Johansson

Arheden

Höglund

et al. 1995

Cytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12 translocations mapped the breakpoints to the centromeres on both chromosomes. The rearrangements were interpreted as the whole-arm translocations der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and AMLL. However, further analysis by metaphase and/or interphase fluorescence in situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all four cases, the corresponding chromosome 7 imbalances differed--monosomy for 7q in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic neoplasms with unbalanced whole-arm or near-centromeric 7;12 translocations and seven dic(7;12) with juxtacentromeric breakpoints have been reported previously: 2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases had loss of 12p material. All but one of the cases with combined 7p and 12p deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid differentiation. No particular clinical, morphologic, or immunophenotypic features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12), often together with 5q deletions, might be associated with previous genotoxic exposure and poor prognosis.