Cryptic ins(4;11)(q21;q23q23) detected by fluorescence in situ hybridization: a variant of t(4;11)(q21;q23) in an infant with a precursor B-cell acute lymphoblastic leukemia report of a second case.

We report the chromosomal findings in a 4-year-old female with precursor B-cell acute lymphoblastic leukemia (ALL). The diagnostic karyotype showed an isochromosome 7q, i(7)(q10), as well as questionable rearrangements on 9p and 11q. Fluorescence in situ hybridization (FISH) studies on both interphase and metaphase cells using the MLL "break-apart" and the centromeric chromosome 4 probes were instrumental in the characterization of an MLL gene rearrangement, which was cryptic by conventional cytogenetic analysis. Specifically, the FISH pattern was consistent with an insertion of the 5' region of the MLL gene into chromosome 4 at band q21, most likely a variant t(4;11)(q21;q23). This is the second case of FISH detection of an ins(4;11) in ALL. Our case exemplifies the importance of FISH in the further characterization of precursor B-cell ALL cases without any apparent prognostically significant chromosomal abnormalities.

Translocon pores in the endoplasmic reticulum are permeable to a neutral, polar molecule.

The pore of the translocon complex in the endoplasmic reticulum (ER) is large enough to be permeated by small molecules, but it is generally believed that permeation is prevented by a barrier at the luminal end of the pore. We tested the hypothesis that 4-methylumbelliferyl alpha-d-glucopyranoside (4MalphaG), a small, neutral dye molecule, cannot permeate an empty translocon pore by measuring its activation by an ER resident alpha-glucosidase, which is dependent on entry into the ER. The basal entry of dye into the ER of broken Chinese hamster ovary-S cells was remarkably high, and it was increased by the addition of puromycin, which purges translocon pores of nascent polypeptides, creating additional empty pores. The basal and puromycin-dependent entries of 4MalphaG were mediated by a common, salt-sensitive pathway that was partially blocked by spermine. A similar activation of 4MalphaG was observed in nystatin-perforated cells, indicating that the entry of 4MalphaG into the ER did not result simply from the loss of cytosolic factors in broken cells. We reject the hypothesis and conclude that a small, neutral molecule can permeate the empty pore of a translocon complex, and we propose that translationally inactive, ribosome-bound translocons could provide a pathway for small molecules to cross the ER membrane.

Translocation (1;17) in accelerating and blast phases of chronic myelogenous leukemia.

A translocation (1;17)(p11;q11) has been observed in two chronic myelogenous leukemia (CML) patients studied during the accelerated or acute stages of their diseases. In a review of the literature, four additional cases of t(1;17)(p11;q11) were identified, suggesting that this marker may be specific for the terminal phase of CML.

Cytogenetics of recurrent abortions.

Chromosome banding studies were carried out on both partners of 37 couples who had had two or more spontaneous abortions. Three patients had chromosome disorders; one was a triple-X female and the other two (one male and one female) were t(13;14) translocation carriers. Review of the literature indicates that the over-all frequency of major chromosome disorders in couples with repeated abortions is 2.6%. About three-fourths of these disorders are reciprocal and Robersonian translocations.