Cancer Genetics and Cytogenetics 165 (2006) 79–80

Letter to the editor

A cryptic chromosome 19 abnormality in a patient withPh-positive acute lymphoblastic leukemia

We would like to draw attention to a new chromosome19 abnormality in a patient with acute lymphoblasticleukemia.

Because chromosome 19 abnormalities may be difficultto detect in leukemias, a fluorescence in situ hybridization(FISH) study was performed using subtelomeric probes inorder to uncover rearrangements of this chromosome inacute B-cell lymphoblastic leukemia (ALL). A series of45 ALLs (34 children and 11 adults) were included inthe study, regardless of the results of conventional bandedchromosome analysis. Six patients exhibited chromosome19 abnormalities: one each with t(11;19)(q23;p13) andt(14;19)(q13;q32), and four with t(1;19)(q23;p13), two bal-anced and two unbalanced translocations. For dual-colorFISH studies, the BAC probes used (Research Genetics, In-vitrogen, Paisley, UK) were RP11-75H6 and RP11-50C6subtelomeric in 19p13.3 and RP11-420P11 and RP11-706G10, subtelomeric on the long arm. The results of FISHstudies were in accordance with the banded karyotypes inpatients with chromosome 19 rearrangements, and the lossof the distal part of 19p was confirmed in the two patientswith unbalanced t(1;19).

0165-4608/06/$ – see front matter � 2006 Elsevier Inc. All rights reserved.

doi:10.1016/j.cancergencyto.2005.06.011

No chromosome 19 abnormality was observed in 38patients, but FISH analysis uncovered a new rearrangementin a 31-year-old female patient with ALL. At diagnosis, inJuly 1994, her leukocyte count was 38 ! 109/L with 90%lymphoblasts. The R-banded karyotype established from anunstimulated blood cell culture for 24 hours was46,XX,t(9;22)(q34;q11)[8]/46,XX[2]. Chemotherapy withmethotrexate and asparaginase was immediately given,but complete remission was not achieved, not even afterreinforcement with cytarabine. Chromosome study per-formed 2 months after the diagnosis showed the presenceof Ph-chromosome-positive mitoses in the bone marrow(2 out of 15 cells), and 18% lymphoblasts were still ob-served in bone marrow. Infectious complications occurredand, in spite of therapeutic changes, the leukocyte countincreased to 30 ! 109/L with 87% lymphoblasts and thepatient was discharged and lost for further follow-up. Thelast white blood count known (March 1995) showed30 ! 109/L.

FISH studies performed on cells collected at diagnosisprior to any treatment, showed two types of cells: normalwith two normal chromosomes 19 (one with a green signal

Fig. 1. FISH of metaphases from the patient using subtelomeric probes for 19p and 19q. (A) Metaphase with two normal chromosomes 19 with signals 19p

and 19q. (B) Metaphase with two abnormal chromosomes 19, one with two 19p probes on each arm and the other with two 19q probes on each arm. Arrows

indicate the Ph chromosomes.

80 Letter to the editor / Cancer Genetics and Cytogenetics 165 (2006) 79–80

on the short arm and one with a red signal on the long arm)in three metaphases and five metaphases PhC with two ab-normal chromosomes 19 (one with a green signal on eachtelomeric region and the other with two red signals onthe telomeric region) (Fig. 1).The rearrangement resembledtwo isochromosomes 19, one for the short arm and theother for the long arm. Two other BAC probes covering the19q13.1 region, RP11-1101H9 (green) and RP11-1050I11(red), were then hybridized to metaphases and showedred and green signals on both arms of only one chromo-some l9, favoring the i(19)(q10) rearrangement. No furtherFISH study could be performed due to the lack of material.Use of a chromosome 19-specific alphoid probe did notshow any abnormality in three analyzable metaphases.

The chromosome 19 rearrangement observed was entire-ly cryptic and detected only by FISH with appropriate mo-lecular probes. In the absence of further FISH studies, themechanism at the origin of the abnormality remains specu-lative. Although centric fission seems the most probableevent responsible for the abnormality, another possibilityis the exchange between the two chromosomes 19 aroundthe centromeric regions. This could be followed by theillegitimate fusion of the chromosome fragments, resultingin isochromosomes for each arm of chromosome 19. Theapparent symmetrical disposition of the probe signals to19q13.1 favors such a rearrangement.

The consequences of the observed structural rearrange-ment are difficult to predict, because there is no obvious un-balanced change and no breakpoint outside the centromeric

region could be ascertained. The abnormality, superim-posed on the Ph-translocation in the patient studied, couldpoint to some chromosomal instability. The abnormalityreported here seems to occur uncommonly, because it wasfound only once in 45 ALLs, but a similar abnormalityon chromosome 20 has previously been reported in one cellof a patient with polycythemia vera [1].

Because the rearrangement cannot be observed withconventional cytogenetic techniques, a systematic searchfor this kind of rearrangement is merited, in order to under-stand the true significance.

Roland BergerMaryvonne BussonINSERM, EMI 0210

Tour Pasteur, Hopital Necker-Enfant Malades149 rue de Sevres

75015 Paris, France

Serge P. RomanaINSERM, EMI 0210

Laboratoire de CytogenetiqueHopital Necker-Enfant Malades

Paris, FranceE-mail address: berger@necker.fr (R. Berger)

Reference

[1] Busson M, Romana S, Nguyen Khac F, Bernard O, Berger R. Cryptic

translocations involving chromosome 20 in polycythemia vera. Ann

Genet 2004;47:365–71.