Document a856QVD2zVV98NapMBdyxbeM

A SIGNIFICANT PROPORTION of patients with various chronic myeloproliferative states develop acute leukemia, including 5% to 6% of patients with polycythemia vera (PV) and 1%to 5% of those with idiopathic myelofibrosis(MF).l4 Clonal karyotypic abnormalities have been demonstrated in the bone marrow cells of some patients with these disorders. Because many of them have received therapy, the role of prior radiation or cytotoxic drug treatment in inducing these changes is uncertain. Several investigators have studied the possible prognostic significance of a clone of karyotypically abnormal cells in patients with these diseases. There are relatively few systematic cytogenetic studies of patients with idiopathic MF or undifferentiated myeloprolifera- From the Department of Medicine,The University of Chicago,Chicago, Illinois. Supported in part by US Department of Energy Contract No.EY 76-C-02-0069and DE-AC02-80EV10360,NCI Grant CA-16910,and the University ofChicago Cancer Research Foundation. * h y o l a University Schoolof Medicine, 2160South First Avenue, Maywood, Illinois. f University of Maryland Cancer Center, 655 West Battimore Street, Baltimore, Maryland. $ Department of Human Genetics, Yale University SchoolofMedi- cine, New Haven, Connecticut. Address for reprints:J. Bruce Miller, MD, Department ofMedicine, Room 0170, Building 103, Loyola University School of Medicine, 2 160 South First Avenue, Maywood, IL 60153. Accepted for publication January 30, 1984. CHROMOSOME ABNORMALITIES M MYELOFIBROSIS Miller el ai. TABLE I. Clinical Characteristics, Treatment Status, and Causes of Death in Eight Patients With PPMF 303 ANLL (7179) 39 63 49 57 51 73 F PV(1/61); PPMF(7/71) "P, busulfan M PV( IO/%); PPMF(9/65) 32P,busulfan M PV(7/67); PPMF(4/76) Busulfan 5682 F PV(4/70); PPMF(6/75) None DMF, CHF (8175) Splenic rupture (8/68) DMF,CHF(8/77) Alive (1183) nt.9 1-6 are Cases IO, 17,23, 19, 30 and 28, respectidy, in 7 posi+ P V polycythemia vera; PPMF postpolyqthemic myelotibrosis;Rx: treatment; ANLL acute nonlymphocyticleukemia; TEM: triethylenemelamine; DMF deteriorating myelofibrosis; CHF congestive heart failure. etic Procedures lase chromosomes were obtained from bone or unstimulated peripheral blood. Recently, in from whom an aspiratecould not be obtained,a n of the bone core biopsy specimen was minced wed for 24 to 48 hours to obtain dividing mye5. Chromosomes were examined with convenLeishman-Giemsa stain, and, in 21of 28 patients, ith the quinacrine banding technique.*For most chromosome counts were obtained from a bumof 20 metaphase cells, 10 of which were phoxi and analyzed in detail. xls for the karyotypic analysis of patients with ogicaldiseaseshave been described previously? nosomes are identified according to the ISCN,'O yotypes are expressed as recommended under m. Results Patient Characteristics PPMF (8 patients): The findings in this group are listed in Table 1. Patients 1 through 6 have been previously reported.' The median age at diagnosisof PV was 50 years, with a median interval to the development of PPMF of 9 years. Prior to the initial cytogenetic study, six of eight patients had been treated with either 32Pand an alkylating agent (four cases) or busulfan alone (two cases). MFIUMPD (20 patients): The characteristics of this group are listed in Table 2. The median age at diagnosis was 62 years. There were no differences in the median age, initial physical findings, or hematologicparameters between the MF and UMPD groups. Of these 20 patients, only 5 had received alkylating agent or radiation therapy prior to cytogenetic analysis (Table 2). !ms of Disease Entities ibrosis (MF) has been defined by the Polycy- Vera Study Group.* Most importantly, none of ntifiable causes of secondardy MF should be Undifferentiated myeloproliferative disease 1) includes the same constellation of findings as he absence of significant fibrosis (less than one the sectionedarea showsfibrosis). Polycythemia 9k used as previously defined.' Postpolycythe- dofibrosis(PPMF)is definedsimilarlyto MFbut subsequent to documented PV. h t i n g myelofibrosis (DMF) is similar to the of agnogenicmyeloid metaplasia as defined by IBlock.' There areincreasing symptomsdue to 'splenomegaly with progressive anemia, leuko- d myeloid immaturity, and often thrombocy'hebone marrow showsa moderate to marked Ithe myeloid serieswith myeloblastsincreased elow that diagnosticof acute nonlymphocytic Survival and Causes of Death There have been seven deaths in the PPMF group, with a median interval of 3.5 years (range, 1-6 years) between the diagnosis of PPMF and death. The major causesof deatharelistedin Table I and includetwocases of acute nonlymphocytic leukemia (ANLL). There have been 17 deaths in the MF/UMPD group, with an average survival of 3 years (range, 1- 18 years) (Table 2). There was one case of ANLL. Overall, 10 patients had complicationsof DMF that contributed to the cause of death. The causes of death were similar for the MF and UMPD subgroups, although the features of DMF were present in 8 of 10 MF patients (3 of whom died within 1 year of diagnosis)but in only 3 of 7 UMPD patients. Results of Cytogenetic Studies The cytogenetic findingsare summarized in Table 3. PPMF: Six of eight (75%) patients with PPMF had 584 CANCER February I 1985 10 48/M MF(2/73) NOM I1 5 I/M MF (1972) Busulfan 12 69/M MF(7/69) None 13 69/M MF (12/72) None 14 67/F MF(3/75) Nom 15 68/M MF (3/75) Busulfan 16 62/M MF(8/74) None 17 65/M MF (1/69) NOM 18 61/M MF(12/66) NODC 19 60/M MF (5/65) NODC 20 53/F MF (4/80) None 21 47/F UMPD (1948) Splenic RT DMF, hemorrhage (5/70) DMF, CHF(5/74) DMF, MI (5/80) Alive (5/80) Colon ca, met to liver (2/77) MI (6/73) DMF, intest infarct (1/70) DMF, infection ( I 1/66) Alive (6/81) DMF, infection (6/77) Splenex. Chloramb Splcnex, busulfan DMF, CHF (3/74) Thyrotoxicosis, CHF (I 1/72) DMF, infection (10/78) Alive (2/82) + + - -abnormal cytogenetic findings either initially or on sub- del(q11). Single instances of 8, 9, 9, 1 Trisomy 1q and a 20q -were each seen in two cases. The two trisomy 1q cases included duplication of q2l-ter and cen-qter. The two patients (Cases 6 and 7)with 20q- were both previously treated and both had respectively. No new abnormalities tient in Case7had an abnormal karyotype( initially (no prior therapy) but during a DMF state after busulfan therapy, a seco I PPMF 01/03/69 BM 28 (17% 0 2 PPMF 09/09/74 PB Z(II) 0 DMF 06/03/77 PB 3 PV 10/26/70 BM 55 (37H 46,XY,-Ell,+E-$iize marI47, , size acrocentric mar PV 07/20/71 BM 107 (26)$ 541 46.XY,-EI l,+E-size mar/47,X, size ac-tric mar PV 08/25/71 BM size acrocentric mar PV 07/26/72 BM PV 01/21/71 BM DMF 01/09/60 BM 4 PPMF 03/13/76 PB PPMF 07/09/76 BM PPMF 07/12/77 PE 6 PPMF 10/12/78 PB 28 (17) 0 ANLL 07/25/79 PB. BM 20 (13) 40 47,X,-X.+2 or 3 mar i CHROMOSOME ABNORMALITIES IN MYELOFIBROSIS Miller et a]. 585 t F i:Q&mt Disease stage / Sample date TABLE 3. (Continued) Sampk source Totalao.of metaphases. Percent abnormalt Abnormal karyotype PPMF 07/02/73 PB patients: PPMF DMF PPMF DMF PPMF DMF DMF DMF ' .' MF MF MF MF MF MF MF MF MF MF MF MF MF DMF (UMPD) UMPD UMPD UMPD UMPD UMPD UMPD UMPD UMPD UMPD MF ANLL 09/01/65 11/27/67 04/27/76 07/29/77 03131/76 0 1/27/76 05/08/74 10/02/74 BM BM BM BM PB RM, PB PB PB 03/28/77 07/29/69 01/26/73 03/02/77 07/13/77 10/24/79 10/30/75 09/24/75 Ol/Op/70 06/19/67 07/18/67 05/27/66 06119/80 01/30/67 07/19/72 05/16/72 08/24/72 02/03/75 03/31/77 04/04/77 09/23/68 10/05/72 01/31/73 08/04/75 04119/76 PB PB PB PB PB PB PB PB PB PB PB BM BM PB BM BM BM BM BM BC,PB BM BM BM PB PB 100 46.XX.42; 1I)(p13;q2I )r/46,XX,-l5,+der(l). t(l;l5~pl~ql?),t(t(z1;l)(p13;q21), del(16)(p12)/5I ,XX.+3,+8,+8?, +C,-15,+ 19,+der( I ) A I ; 15Mpl?;ql?), t(Z; 11Xpl3;q21),del( I6Xpl2) 50 46,XY.Fq100 46,XY,deI(2O)(ql I ) 25 46.XYAW 1Xq421) 69 46,XYAeK 1Mq42?)[8%W 46,XY,dcl(2O)(ql I)[62%] 0 60 46,XX4,+der(6).t( 1;6XqZS:p25?) 100 46,XY&I( 12xq141921) 100 46,XY&l( I 2)(ql4?q2 1)[56%y '5I,XY.+Y,+8.+8,+12,+19, dd(l2)(ql4?q2 1)[44%] 57 46,XY.-2.-a,+der(2),1(2;6Mq371;q 15'0, , +1(6)@25?q 157) 10 0 33 46,XX.del(l3)(ql l?q14?) 50 46,XX,del(l3)(qI 1?q14?) 53 46,XX,de1(13Xql1?q14?) 100 47,XY,+8,del(5)(q3 I ) 100 46,XY,t(6; I2)(6pte~-6q23?: I2ql3?- 12qtec 12pler-.I2q13?) 0 0 0 -0 27 47,XX.+2O,dup(5)(pter q33?::q22?-qtei 100 46,XX,-A2,+mad 0 92 47,XY,+D 81 47,XY,+14 93 45.X,-Y 5 5 0 78 47,xx.+G,Bq100 46,XX,de1(5)(q15)/47,XX,+2 I,del(5)(ql5) 83 47,XX,+2 l,dcl(5)(q15) 100 47,XX,+2 I.dcl(5Xq 15) Sr in parentheses indicate subtotal of metaphases examined in detail fluorrrence, unless marked with#, in which case the subtotal is r ofm e t a p b analyzed with conventional Giemsa stain. d percentage of metaphases examined with fluorescence or, if ? w i n g was not done, calculated as percentage of cells analyzed with in only. p(upe seen in only a single-banded cell from this sample. !cB only the clone with 47 chromoroma since the abnormality diploid clone could not k accurately scored in many cells without techniques. 1A constitutional abnormality also observed in stimulated lymphocytes from this patient. LA metacentric B4.e marker &My resulting from a translocation betwen no. 2 and a C-gmup chromosome. ** Five other cells analyzed with conventional Giemsa only were all normal. PPMF: postpolycythemia fibrosis; BM: bone marrow aspirate; P B peripheral blood (without phytohcmagglutin); DMF: deteriorating myelofibrosis: P V polycythemia vera:ANLL: acute nonlymphocytickukemia; M E myelofibrosis: UMPD: undifferentiated myeloproliferative disorder; BC: bone core biopsy. !MI abnormality appeared (46,XY,2Oq-). The 4 had a normal karyotypeon 4 occasions rS after the onset of PPMF but then developed mal clone (47,X,- X,+ 2 or 3 markers) coinci- 'transformation to ANLL. Therefore, both pa- hPPMFand subsequentANLL (Cases 3and 4) oncornitant changes in their karyotypes. UZ3 Group: The results of cytogenetic studies 'UP are detailed in Table 3. Of the entiregroup of20 patients, 11(55%) hadkaryotypicabnormalities.In the MF and UMPD subsets, 7 of 12 (58%) and 4 of 8 (50%)patients were abnormal, respectively. Three patients had abnormalitiesof 5q (Cases 15,20, and 28); twoinvolved a deletionwith loss of the long arm distal to q 15 or q31 (Figs. 1 and 2A). In the third case, there was a duplication of q22 to q33 (Fig. 2B). Three cases had a translocation involving no. 6; one (Case 9) affectedthe shortarm and two(Cases 11and 16)the long 586 CANCER February I 1985 FIG. 1. Karyotype of a Q-banded metaphasecell obtained from Patient28. The cell containsa partial deletion of the long arm of del(5)(q1 9 , and an extra no. 2I . There is also a loss of one no. 9, which was observed in this cell only. Chromosomal abnormali arrows. t arm (Fig. 3). In one patient (Case 16) it appeared that types, although the single case of ANLL (Fre 6q23 to q terminal (qter)was missing; in another (Case can-British [FAB] classification M2) was 1l), part of no. 6 was translocated to 2q and the re- abnormal group. The histologic division be mainder formed a ring chromosome. In both Cases 9 and UMPD did not correlate with aneuplo and 11, a break occurred in 6p25 with probable loss of Only 5 of 20 patients with MF or UMP 6p25 to 6pter. Two patients (Cases 10and 16)had aber- toxic drug or radiation therapy prior to rations of 12q; one involved an interstitial deletion study. Only the patient in Case 9 was heavily (q14?q21) and the other a translocation with a break in whereas the other four had relatively brief co s 12q13?(Figs. 4A and 4B). Due to the uncertainty of the alkylating agent therapy shortly before chro breakpoints, these could be in the same band of no. 12. analysis. There was no correlation between pfi0 Trisomy for lq (Fig. 3) and deletion of 13q were each ment and the frequency of abnormal karyotype, noted in one case. A gain of No. 8 was noted twice, once of 15 ( 5390)of the untreatedgroup and 3 of 5 (60 (Case 10)as part of an evolutionofthe karyotype(Fig.4). treated patients being abnormal. The latter patient was the only one whose karyotype The one patient who developed clearcut AN evolved in this group, and this change was associated 28) was unusual in appearing initially with sev with a progressively deteriorating clinical course of mia and a marrow showingearly MFbut mo DMF. A gain of 14,20, or 21,and a loss of Y each were a severe erythroid hypoplasia. Her initial c observed in single patients. sample and three additional ones o Clinical correlates:The survival, causes of death, and until her death showed the same the proportion of patients developing DMF were gener- (47,XX,+ 21,5q-) (Fig. 1). Durin ally similar for those with normal or abnormal karyo- row showed progressive fibrosis with increasing CHROMOSOME ABNORMALITIES IN MYELOFIBROSIS akaryocytic hyperplasia. She then developed nia and one year later evolved into frank e had never received any cytotoxic therapy. Discussion Miller et al. 587 ical observations: The age distribution and clini- of our PPMF group were indistinguishable f our patients with MF or UMPD, and the previous diagnosis of PV was essential tiating between them. In our study, the overall of ANLL in PV is 14% ( 5 of 36 cases),' of 8 patients (25%) in the subgroup with veloped AWL. These findings are in general t with those of Silverman et aL2who reported lence of ANLL in patients with PV, whereas 5 %I in their PPMJ? series subsequently trans- D- ietic studies: Six of eight (75%) patients with had either initially or subsequently chromosomal ialities. Only the abnormalities in Case 3 (tnq and trisomy 9) were found without the back- prior therapy. Both of these findingshavebeen in polycythemic phase PV patients.I3 mosome gains and losses in ten cases of FIGS. 2A AND 2B. (A) Chromosome pair no. 5 from a Q-banded metaphase cell from Patient 15. There is a partial deletion of the long +arm of one no. 5, de1(5)(q31).(B) Chromosome pair no. 5 from a Q-bandedcell fromPatient 20. The 5q isthe resultofa duplicationof part of the long arm of no. 5, dup (5)(pterq33?::q22?+qter). karyotypic abnormalities collected from a literat~re'~a-r~e'summarized in the histoigure 5. Eight of these ten individuals had un- MF and UMPD nor therapy. Table 4 summarizesthe findings Clinical characteristics:Sixty percent of our patients review when added to those of the current had MF and 40% had UMPD. The initial clinical char- a total of 16 PPMF patients). acteristicswere not clearly differentbetween the MF and finding of 5q- appears to be a frequent ab- UMPD subsets,although there was a suggestion that the associated with the terminal stages of PV,7922 MF subset developed DMF more frequently.The causes in association with other karyotypic abnor- of death and the frequency of leukemic transformation e previously reported the appearanceof 5q - (1of 20 patients(5%)) were similarto previousreports, in ents, seen concomitant with transformation which 2-5% of patients with MF have developed in three and as an evolutionary change in one ANLL.3*4*26 after therapy.' However, three patients, all Cytogeneticjindings in MFfUMPD: Eleven of our 20 significant prior treatment for PV, have been patients (55%) with MF or UMPD had abnormal karyo- DMF to have the late appearance of types. There were no clinical differences or prognostic ANLL.5 significance associated with aneuploidy. These findings PV indicate that the incidence of are in agreement with Whang Peng et al., who reported ties is higher in treated patients an incidence of cytogenetic abnormality of 64% upon ewly diagnosed ones, and that the types of initial study of patients with MF.27 8 differbetween these two groups. Changes seen Previous reports have presented a wide array of ab- therapy involved hyperdiploidy, often due to normal karyotypes in MF and UMPD. The chromo- bf 8 or 9, whereas changes seen after extensive &toften involve structural rearrangement of chro- (20q-, trisomy 1q).6,22,23Our two patients somal abnormalities in 36 cases of MF or UMPD collected from the literature are shown in the histogram of Figure 5.13,19,16,17,20.21.24,25,27,28,28a-28h Whenever possible ihsformedto ANLL had karyotype changesasso- the published karyotypes have been reviewed by us to h hthis event. This is consistent with earlier re- identify the breakpoints of structural changes. Three kt the finding of karyotypic abnormalities in PV cases of idiopathic thrombocythemia (IT), a disorder isnot necessarilya poor prognostic sign,but that closely related to UMPD, are included. One patient with uent deveiopment of abnormalities in ini- IT was found to have both trisomy 8 and trisomy 9, one malpatients often carries a poor p r o g n ~ s i s . ~ ~w. ~as~a 60-year-old man with loss of the Y chromosome, 588 CANCER February 1 1985 FU3. 3. Karyotype of a Q-banded metaphase cell obtained from patient 9. There is a rearrangement(arrow) between chromosomes resulting in trisomy of a portion of Iq. [46,XX,-6,+der(6),t(1;6)(q25;p25?)]. 9 and the third had a rearrangement ofthe longarm of No. 5 leading to 5q-. When the results of our current study (1 1 aneuploid patients) are added to these 36 cases, the following abnorrnd'ties (with at least 2 cases of each) were found in order of decreasing frequency: trisomy 8 +(10cases),trisomy 1q (8 cases), loss of 5 or 5q -( 5 cases) or 5q (1 case), loss of 7 or 7q - ( 5 cases, 1 of which is iseries had received prior cytotoxic therapy. there was no apparent correlation of karyotypi' malities with prior cytotoxic treatment. Ho analyzed more closely those patients with 1< 5q - and/or loss of 7 or 7q -, since recently genetic findings have been reported to be strongly with either previous cytotoxic the both -7 and 7q-), trisomy 9 (4 cases), trisomy 21 (4 cases), loss of Y (4 cases), 15q-, (3 cases), 20q- (3 +cases),6p-(3cases, all involvinga translocationleading to trisomy 1q) and 17p (2 cases). In the current series,the lossof the Y chromosomewas found in the initial studyof a 70-year-old man who never developed ANLL. The loss of the Y chromosome in elderly males may be unrelated to hematologic disease.29*O30ur review of the literature revealed three additional MF cases with loss of the Y chromosome in previously untreated males who tended to be younger than previously noted (ages of 49, 60, and 61 years, respec- vious occupational exposureto chemicalsolvents, ticides, or other potential mutagens, and the s u b development of preleukemic syndromes or A m Although only 9 of47 patients (19%)with MForI shown in Table 4 had partial or total losses o somes 5 or 7 , 4 of these 9 (44%)had prio either radiotherapy (2 cases: 1 for prostati and 1 for Hodgkin's disease25),busulfan Case 15), or benzene and other petroleum s case)27.Of the 38 MF/UMPD patients with ka abnormalities other than losses of chromosom only 6 (16%) had prior cytotoxic therapy or tively). exposure. This suggests an association of prior Of the 36 cases collectedfrom the literature, 27 had no with the occuTence of these specific karyotypi prior treatment, 3 had received prior cytotoxic therapy, and the status of 6 could not be ascertainedfrom the data provided. Only 3 of the 11 patients from the current malities in patients with MF or UMPD. Trisomy 1q of variousderivationsisa freque in MF and UMPD (Fig. 5). Nowell14describe .CHROMOSOME ABNORMALITIES IN MYELOFIBROSIS Miller et a/. / 589 23 5 8 7 8 9 IO i II I( I2 I4 15 20 16 17 r1) * 4 21 22 18 XY patients with MF. Hsu et al. have reported a somy l q (46,XX,- 6,+der(6),t( 1;6)(q25;p22) t with deteriorating MF without frank ytogenetic findingsimilar to that in our Case et al. also reported a similar abnormality 6 +der(6),t( 1;6)(q25;p21) in a patient with idly evolved into ANLL without radiother- oxic drugs ever having been given.28Gerescribed three individuals with DMF (one opathic and two with PPMF), all of whom had trisomy lq and monosomy 7q with identical transloca- tions between chromosomes 1 and 7.20 A more detailed analysis of the region of lq that is trisomic in the 7 patients with PPMF and in the 8 patients with MF/UMPD showsthat all 15 are trisomic for bands lq25 to lq32, in accord with the observations of R ~ w l e yO.n~e~patient is trisomic for all of No. 1, and 12 patients are trisomic for part of no. 1 as the result of an unbalanced translocation of no. 1 from the breakpoint (p22 to q25) to the end of the long arm. Two other 590 CANCER February I 1985 IO - s 8- E$: V gw 2- 016 cmes PPMF I3 Treated 047ccbes MF/UMPD 0 Dektion 0 Trisomy 8 Treated ~ n a kin p+ dektion of q in p+ trisomy fw q . . .m r n n I 2 3 4 5 6 7 8 9 IO II 12 I3 14 I5 16 17 18 192021 22 X Y n CHROMOSOME NUMBER n ET- 14' FIG. 5. Histogram of clonal karyotypicchanges (gains, losses, and rearrangements)seen in 16 PPMF and 47 MF/UMPD patients. Each box represents a clonal change seen in a single patient. Comparison of the PPMF and MF/UMPD Although in many instances the c h changesin PPMFas well asin MF and UMPD be nonrandom, specific chromosome abnom diagnostic patterns that clearly distinguished eases were not apparent (Table 4). The q changes associated with MF seem to be distributedamong the various chromosom seen in PPMF. Some differences in the frequency are seen, however. Trisomy 8 is the o more common in MF/UMPD than in PP incidence of trisomy 8 in PPMF (usually j treated) and in secondary ANLL" are unexp- thqmay implythat prior therapy isnot relatedto ance of trisomy 8 in these disorders.This also be true in our serieswith MF/UMPD. Trisomy9i to be more common in all phases of PV (un 23%= PPMF-31% (Table 4); leukemic 23%=) than in MF/UMPD (9%, Table4). War malities were also more common in PPMF, 20q -,loss of 7or 7q -,and,to a lesserextent and 5q-. Cytogeneticabnormalitiesdo not provide a pattern or prognostic usefulness in MF/UMPS Wqinitial studies in PPMF. Partial chromosomes, particularly nos. 5orocro7m,palreete..., with prior therapy or chemical exposure in PPMF does appear to have a higher tendency1 leukemic transformation than does MF, and an' tion in karyotypeappearsto have seriousprognd Dlications in PPMF in remrds to this transitiod patients (both with MF) have an internalrearrangement of no. 1 resulting in a duplication of the same segment, namely lq21 to lq32. Although 20q -appearsto be more frequentin PPMF (Table 4), three groups have $.epor&edde12qq11) in pa- tients with MF. One case with early DMF showed the deletion after 5 years of busulfan therapy." Findley et al.= and Kondo et aL3' each described a 2Oq- in patients who had never received any cytotoxictherapy. No ANLL developed during follow-up in either patient. REFERENCES & WB.Myeloid metaplasia: AL, Linman JW. Idio metaplasia:Its evolution into acute leukemia.Arch Intent M 132:709- 7 12. ! 5. Berk PD, GoldbergJD, SilversteinMN et al. Increasedb 1 J TABLE 4. Common Clonal Karyotypic Abnormalities in PPMF (16 Cases) and MF/UMPD (47 Cases) Chromosome aberrations No. of patients (percent) Disease +h -5159- -7llq- +8 d+9 2oq- PPMF (16 cases) MF/UMPD (47 we^) 7 (44%) 8 (17%) 3 (19%) 5 ( I 1%) 5 (31%) 5 (11%) 1 (6%) 10 d l % , 5 (31%) 4 (%) 3 (1WI 3 (6%) PPMF postpolycythemia myelofibrosis;MF/UMR): myelofibrosis/undifferentiatedmyeloproliferativedisorder. CHROMOSOME ABNORMALITIES INMYELOFIBROSIS Miller et al. 59 1 -- ,Kanofsky JR, Rowley JD, Baron JM, Vardiman JW. clinical significanceof cytogenetic abnormalitiesin polyAm JHematol 1981; 11:29-45. rson T, Zech L, Johansen C, Modest U.Identification of Ichromosomes by DNA-binding fluorescent agents. Chromo- ,Rowley JD. Chromosomesin leukemia and lymphoma emphasison methodology. In: Catavsky D, ed. The Leu- Pell.New York Churchill-Livingston, 1981; 184-202. ISCN.An internationalsystem for human cytogeneticnomen- -0 J. Myeloproliferative disorders (MPD): Myelofibrosis, msis,extramedullaryhematopoiesis,undifferentiated MPD, Drrhagic thrombocythemia. Semin Hematol 1975; 12:409- t JR,Kanofsky JR, Rowl& JD, Baron JM. Multiplecyto- abnormal clones in two polycythemia vera patients. P. F& J. chromosome studiesin preleukemic states: krative versus cytopenic disorders. Cancer 1978; -2261. UI den Berghe H, Orshoven AB, Louwagie A, VeMrilghen R, 3. Sokal G. Transformationof polycythemiavera to myelofi- I U ~ Y FP,inchiarolli D, Gilbert HS,Wittman R, Hirschhorn 1trisomy of the long arm of chromosome 1 in myelofibrosis , :miavera. Am JHematoll977; 2:375-383. -noSI, Van den Berghe H, SandbergAA. Chromosomesand Iof human cancer and leukemia: XXXI. Dq deletionsand cance in proliferative disorders. Cancer 1979; 43:1350- :Id V,Price TH,Adamson JW, Fialkow PJ. 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