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Inhibition of apoptosis in stage a chronic lymphocytic leukemia is reversed by acyclovir
Biomed
& Pharrnacother
1998 0
Advances
in Management
G) Infection
Deletion of the nonlyn~phocytlc PTripputi,T University lC6,20052
Coliva
long arm leukemia
of cbrornosonre 1 in and in nryelodysplnstlc
,R Chie.sa,D
of Milan, Istituto Monu, Italy.
Cigognini,
di Scienze
B Forgione
Biomediche
and G Cornea.
San Gerardo.via
(CNR-Rome)
Paris
Disease
INHIBITION LYMPHOCYTIC P Trippuli, G Cornco.
OF APOPTOSIS LEUKEMIA
R Chiesa. T Coliva,
IN STAGE A IS REVERSED D Cigognini,
CHRONIC BY ACYCLOVIR
B Forgione,
P Pioltelli
and
Donizelti
Monosomy of chromosome (ch) 7 or partial deletion of the long amt of cb 7 is frequently observed in myelodysplastic syndromes (MDS) and secondary acute nonlymphocytic leukemia (ANLL), seen in patients with previous exposure to mlltagenic agents or radiailon therapy.These chromosomal abnoi IIIP~LICS have been associated with a rapid progression or the discasc :ud il poor response to thenpy.The deletions have been described in at least three regions of ch 7 : 7q22, 7q3 1.1-32 and 7q3G. The cell origin or MDS and ANLL could bc cilhcr the CFU-GEMM slcm ccl1 or the olurioolcnt Stern ccll,but ncithcr of lhcsc possibilitiw hm yet been provcn.Tlic ah&x or the deletion in DNAs cxlracted by peripheral lymphocylcs argues against a multipotent stem cell origin, so, we were very carerully lo separe lymphocyles from mveloid cells and we refer to IvmDhwvtw as normal cells. 147 ~atienls whith iNLL,MDS and MPD were &died f&r molecular deletions of ihe long arm or ch 7.24 patients were secondary ANLL. 43 MDS. 30 de nova ANLL and 50 MDP mostly CML.TE, PV and MF.Periphersl blood cells fmm these patients were separated in lymphocytes and myeloid cells by mini mats columns and monoclonal antibodies for the myeloid antigens CD15 and CD33. Afler microscopical examination of the Giemsa colored smears to detect cell separation , more than 95% myelo or monocytic cells was requested to include these samples as “tumor cells” , normal cells were obtained with less restricted criteria and were mostly rapresented by lymphocyte&We detecled the loss of heterozigosity in the long arm arch 7 in row patients arfected by secondary acute my&id leukemia and tnyelodisplasia. We used PCR and Southern blotting hybridization with polymorphic DNA fragments. Monosomy of chromosome 7 has been detected in two more patients by cytogenetics. The deletions have been mapped respectively in the region 7q22 for one patient and in 7q31-32 for three more patients. In these4 patients the d&lions slart in the CFU-GBMM stem cell or in a moic committed stem ccl1 ns show by the absence ol tw deletion in the DNAs extracted by peripheral lymphocytes. In the 7. patients with monosomy or chromosome 7 also lymphocytes and consequently a totipotent stem dell are involved. Acknowledgment This work was supported by grants from project ACRO from the University or Milan.
Elsevier.
of Malignancies
and Neoplastic
secondary ocutc slndromcs.
; 52 : 343-344
and
UiivcrsilyoiMilan, lstitutodi Scicnzc Biomedichc Via Donizelti 10620052 Monza, Italy.
San Gerardo
Chronic lymphocytic leukemia (CLL) is n clonel malignant disease of bone n~~wow B-lymphocytes, due to an increased survival, rnthcr than an increased ccIIu!x prolXcr?lion, caused hy an inhlhilion of applosis or lxogi~uwul cell dcilth. WC carried Out an invcsQalion regarding clinical da& cytogcnclic illbri~tions. in vitro lymphocytes survival, apoplosis and induction 01’apoptosis with dil’l’crcnt drugs. 64 pJtienls arfcctcd by B-CLL, have been divided according to Binet classification in stages A.B and C. In stngc A we round B small group or patienls with an excellent prognosis. lack or cytogenelics nbcrratian, longtcnn survival in tissue cullurc and slrongly inhibited apoplosis. Lyn~phocylcs wcrc licoll-purified from peripheral blood Pod cultured in vitro. DNA was extracted and then run on a 2% agwosc gel with il marker DNA made or a ladder of 100 bp polymers to check for multimcrs of 180 bp typical ol npoplosis. We have also checked this lack of apoptosis in the clinical course of tbc discasc in one patient over a five year period, respectively 13.15 and 17 years since the beginning of the disease, no apoptosis was present. The palient that WC studred shows some peculiar aspects : high level of Icucccytcs, (range 150-250.000) in the lnst 5 years. He had also a significant decrease or lymphocytes From 25O.CXX to 15O.OXI after an injection of a vaccine against influcntia. Hc was allso treated with low doses olalfa-interreron (l.CCO.ooO U 2-3 times for week) with a marked decrew or the leucocytes.On lhe basis ol these clinical results, apparent response to influentia vxcilie and inwferon, with dccrca.seoTperipheral blood leucocytes and complete inhibition olapoptosis in yltro, we wanted to determine whether any drug could interpherc wilh the lack of apoptos~ Therefore WC added 50 ug/ml or Acyclovir to the a 1 week old lymphocytes culture and we extracted the DNA after 3 days.The result obtained appears to indicate that, at least in this single patient, acyclovir can induce lymphocytes apopt*s,s. Indeed ,!‘C treatct1 a few CLL pntients h Firrim srmpicx mlectlon w~ith Acyciol il and wc found: 3 out 01 IU patwnts had n significant decrease of the number of leucocytcs.This seems to occur only in a small group of CLL patients as shown by a study made on 10 palicnts with olher hematological malignances,also treated with Acyclovir with no leucopenic cfrect. Acknowledgement This work was supported
by a grant from project ACRO of CNR, Rome.
& Pharrnacother
1998 0
Advances
in Management
G) Infection
Deletion of the nonlyn~phocytlc PTripputi,T University lC6,20052
Coliva
long arm leukemia
of cbrornosonre 1 in and in nryelodysplnstlc
,R Chie.sa,D
of Milan, Istituto Monu, Italy.
Cigognini,
di Scienze
B Forgione
Biomediche
and G Cornea.
San Gerardo.via
(CNR-Rome)
Paris
Disease
INHIBITION LYMPHOCYTIC P Trippuli, G Cornco.
OF APOPTOSIS LEUKEMIA
R Chiesa. T Coliva,
IN STAGE A IS REVERSED D Cigognini,
CHRONIC BY ACYCLOVIR
B Forgione,
P Pioltelli
and
Donizelti
Monosomy of chromosome (ch) 7 or partial deletion of the long amt of cb 7 is frequently observed in myelodysplastic syndromes (MDS) and secondary acute nonlymphocytic leukemia (ANLL), seen in patients with previous exposure to mlltagenic agents or radiailon therapy.These chromosomal abnoi IIIP~LICS have been associated with a rapid progression or the discasc :ud il poor response to thenpy.The deletions have been described in at least three regions of ch 7 : 7q22, 7q3 1.1-32 and 7q3G. The cell origin or MDS and ANLL could bc cilhcr the CFU-GEMM slcm ccl1 or the olurioolcnt Stern ccll,but ncithcr of lhcsc possibilitiw hm yet been provcn.Tlic ah&x or the deletion in DNAs cxlracted by peripheral lymphocylcs argues against a multipotent stem cell origin, so, we were very carerully lo separe lymphocyles from mveloid cells and we refer to IvmDhwvtw as normal cells. 147 ~atienls whith iNLL,MDS and MPD were &died f&r molecular deletions of ihe long arm or ch 7.24 patients were secondary ANLL. 43 MDS. 30 de nova ANLL and 50 MDP mostly CML.TE, PV and MF.Periphersl blood cells fmm these patients were separated in lymphocytes and myeloid cells by mini mats columns and monoclonal antibodies for the myeloid antigens CD15 and CD33. Afler microscopical examination of the Giemsa colored smears to detect cell separation , more than 95% myelo or monocytic cells was requested to include these samples as “tumor cells” , normal cells were obtained with less restricted criteria and were mostly rapresented by lymphocyte&We detecled the loss of heterozigosity in the long arm arch 7 in row patients arfected by secondary acute my&id leukemia and tnyelodisplasia. We used PCR and Southern blotting hybridization with polymorphic DNA fragments. Monosomy of chromosome 7 has been detected in two more patients by cytogenetics. The deletions have been mapped respectively in the region 7q22 for one patient and in 7q31-32 for three more patients. In these4 patients the d&lions slart in the CFU-GBMM stem cell or in a moic committed stem ccl1 ns show by the absence ol tw deletion in the DNAs extracted by peripheral lymphocytes. In the 7. patients with monosomy or chromosome 7 also lymphocytes and consequently a totipotent stem dell are involved. Acknowledgment This work was supported by grants from project ACRO from the University or Milan.
Elsevier.
of Malignancies
and Neoplastic
secondary ocutc slndromcs.
; 52 : 343-344
and
UiivcrsilyoiMilan, lstitutodi Scicnzc Biomedichc Via Donizelti 10620052 Monza, Italy.
San Gerardo
Chronic lymphocytic leukemia (CLL) is n clonel malignant disease of bone n~~wow B-lymphocytes, due to an increased survival, rnthcr than an increased ccIIu!x prolXcr?lion, caused hy an inhlhilion of applosis or lxogi~uwul cell dcilth. WC carried Out an invcsQalion regarding clinical da& cytogcnclic illbri~tions. in vitro lymphocytes survival, apoplosis and induction 01’apoptosis with dil’l’crcnt drugs. 64 pJtienls arfcctcd by B-CLL, have been divided according to Binet classification in stages A.B and C. In stngc A we round B small group or patienls with an excellent prognosis. lack or cytogenelics nbcrratian, longtcnn survival in tissue cullurc and slrongly inhibited apoplosis. Lyn~phocylcs wcrc licoll-purified from peripheral blood Pod cultured in vitro. DNA was extracted and then run on a 2% agwosc gel with il marker DNA made or a ladder of 100 bp polymers to check for multimcrs of 180 bp typical ol npoplosis. We have also checked this lack of apoptosis in the clinical course of tbc discasc in one patient over a five year period, respectively 13.15 and 17 years since the beginning of the disease, no apoptosis was present. The palient that WC studred shows some peculiar aspects : high level of Icucccytcs, (range 150-250.000) in the lnst 5 years. He had also a significant decrease or lymphocytes From 25O.CXX to 15O.OXI after an injection of a vaccine against influcntia. Hc was allso treated with low doses olalfa-interreron (l.CCO.ooO U 2-3 times for week) with a marked decrew or the leucocytes.On lhe basis ol these clinical results, apparent response to influentia vxcilie and inwferon, with dccrca.seoTperipheral blood leucocytes and complete inhibition olapoptosis in yltro, we wanted to determine whether any drug could interpherc wilh the lack of apoptos~ Therefore WC added 50 ug/ml or Acyclovir to the a 1 week old lymphocytes culture and we extracted the DNA after 3 days.The result obtained appears to indicate that, at least in this single patient, acyclovir can induce lymphocytes apopt*s,s. Indeed ,!‘C treatct1 a few CLL pntients h Firrim srmpicx mlectlon w~ith Acyciol il and wc found: 3 out 01 IU patwnts had n significant decrease of the number of leucocytcs.This seems to occur only in a small group of CLL patients as shown by a study made on 10 palicnts with olher hematological malignances,also treated with Acyclovir with no leucopenic cfrect. Acknowledgement This work was supported
by a grant from project ACRO of CNR, Rome.