Chromosome aberrations in CD34-positive acute myeloid leukemia. Correlation with clinicopathologic features

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Myeloid Leukemia

Correlation with Clinicopathologic Features

Franca Fagioli, Antonio Cuneo, Maria Gretel Carli, Antonella Bardi,

Nadia Piva, Rita Previati, Gian Matteo Rigolin, Luisa Ferrari,

Romedio Spanedda, and Gianluigi Castoldi

ABSTRACT: Morphologic, immunologic, and cytogenetic features were studied in 30 newly diagnosed patients with CD34-positive (CD34 +) de nova acute myeloid leukemia (AML) in comparison with 30 pa- tients with CD34-negative (CD34 - ) AML. Karyotype at diagnosis was abnormal in 25/30 CD34 + AML pa- tients, of which nine had major karyotype aberrations (MAKA). Clonol chromosome changes were de- tected in 9/30 patients with CD34 - AML. The most frequent chromosome aberration in CD34 + patients was -5/5q - , an aberration showing a strong association with the M2 FAB subtype of AML. Other recur-

ring chromosome changes involved chromosome 16q (four cases) and chromosome 17p (three cases). Total

or partial monosomy 7q was detected in three cases. Among CD34 - AML, two patients had the classical t(15;17) and two had structural aberrations of 6q. Among patients with CD34 + AML, nine had M A K A in association with trilineage myelodysplasia (TMDS). TMDS was infrequent in CD34 + AML w/thout MAKA and in CD34- AML. Complete remission (CR) was achieved in 8/30 CD34+ AML (26%), as compared with 22/30 CD34- AML (73%), and m e d i a n survival was 2 months in the former group and 8 months

in the latter. No patient with CD34 + A M L and MAKA achieved CR, whereas 8/21 CD34 + AML without complex chromosome changes or with normal karyotype achieved CR.

In conclusion, a distinct cytogenetic profile m a y be associated with CD34 + AML. Cytogenetic findings in CD34 + AML m a y be clinically relevant in that they may disclose a subset of patients with M A K A with

a low CR rate.

INTRODUCTION

The CD34 monoclonal antibody detects a 110-115 kD membrane glycopmtein present on 1-2 % of normal bone marrow cells, including unipotent and multipotent progenitors [1, 2]. CD34 expression is higher on early progenitor cells and tends to decrease progressively with maturation [3].

In order to better understand the clinico-biologic sig- nificance of CD34 positivity in acute leukemia, growing at- tention has been devoted over the last 5 years to the presence of CD34 + blast cells in acute myeloid leukemia (AML), high- lighting some important cytogenetic and clinical correlations in this immunologic subset of AML [4-6].

This stage-specific marker was found in 40-50% of AML cases, possibly identifying a subset of patients with a low remission induction rate. Patients with CD34 + AML have been frequently shown to fall within the M1-M2 category of From the Institute of Hematology, University of Fermra, Italy

Address reprint requests to: Prof. Gianluigi Castoldi, Institute of Hematology, Via Savonarola 9, 44100 Ferrora, Italy.

Received March 3, 1993; accepted July 15, 1993.

the FAB classification and to carry clonal abnormalities involving the long arm of chromosome 7 [4, 5].

To further analyze the cytogenetic and clinicopathologic features of CD34 + AML, we performed morphologic, immunologic, and cytogenetic (MIC) studies in 60 newly diagnosed adult AML patients, 30 of whom expressed the CD34 antigen in more than 20% blast cells.

PATIENTS AND METHODS

Sixty patients with de nova AML, seen at our Institution be- tween January 1988 and July 1992, are included in the present report. Bone marrow (BM} smears were available for review in all cases. Immunologic and cytogenetic analysis were performed successfully at diagnosis. The patients were divided into two groups according to the positivity or nega- tivity for the CD34 stem cell marker.

Cytologic Studies

Morphology: Patients were classified according to the FAB criteria [7]. Bone marrow smears were reviewed to assess the presence of myelodysplastic features. According to previously 119

Cancer Genet Cylogenet 71:119-124 (1993) 0165-4608/93/$06.00

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120 F. Fagioli et al. p r o p o s e d criteria [8, 9], trilineage m y e l o d y s p l a s i a (TMDS)

was defined by the p r e s e n c e of more t h a n 25% dysplastic erythroblasts and more than 50% abnormal granulocytes and megakaryocytes.

Immunophenotyping:

BM c y t o s p i n p r e p a r a t i o n s a n d / o r pe- ripheral blood smears were stained by an i m m u n o c y t o c h e m - ical m e t h o d using alkaline p h o s p h a t a s e - a n t i - a l k a l i n e phosphatase (APAAP) complexes [101. To minimize Fc nonspecffic binding, the slides were p r e - i n c u b a t e d w i t h rabbit s e r u m (Dakopatts, Copenhagen, Denmark). Reactivity was tested to a p a n e l of m o n o c l o n a l a n t i b o d i e s p u r c h a s e d from various firms: stem cell marker: HPCA-1 (CD34); myeloid-associated markers: LeuM1 (CD15) (Becton-Dickinson, M o u n t a i n View, CA); My9 (CD33), My7 (CD13), My4 (CD14) (Coulter Inc., Hia- leah, FL), GplIb/IIIA (CD41a) (Dakopatts, Copenhagen, Den- mark); l y m p h o i d - a s s o c i a t e d markers: Leu12 (CD19) (Becton- Dickinson), OKBCalla (CD10), OKT16 (CD7), O K T l l (CD2) (Ortho Diagnostic System Inc., Raritan, NJ).

Cytogenetic Studies

C h r o m o s o m e analysis was p e r f o r m e d at initial p r e s e n t a t i o n in all patients. BM s a m p l e s were cultured for 24 and 48 hours w i t h o u t mitogens. S y n c h r o n i z a t i o n w i t h methotrexate a n d t h y m i d i n e was performed. Metaphases were G-banded w i t h Wright stain [10]. C h r o m o s o m e aberrations were d e s c r i b e d according to the International System for H u m a n Cytogenetic N o m e n c l a t u r e (ISCN) [11]. The p r e s e n c e of three or m o r e events of t r a n s l o c a t i o n or n o n - d i s j u n c t i o n in the s a m e clone was defined as "major karyotype aberration" (MAKA). Mi- nor karyotype aberration (MIKA) was d e f i n e d by one or two such events [12].

Clinical Studies

Salient clinical features at p r e s e n t a t i o n , o u t c o m e of remission i n d u c t i o n therapy, and survival were analyzed in all patients.

RESULTS

Thirty patients (50%) had more than 20% blast cells expressing the CD34 antigen. Positivity for the anti-CD34 monoclonal a n t i b o d y was less t h a n 3% in the blast cells of 30 patients, here referred to as C D 3 4 - .

Cytologic Studies

FAB subtypes in CD34 + a n d CD34 - are detailed in Table 1. The M2 FAB s u b t y p e was found m o r e frequently among CD34 + patients (12/30) t h a n among CD34 - patients [2/30). Conversely, the M5 FAB s u b t y p e was f o u n d in 4/30 CD34 + patients versus 11/30 C D 3 4 - patients.

M o r p h o l o g i c a b n o r m a l i t i e s affecting m u l t i p l e cell lin- eages, fulfilling the stringent criteria for the diagnosis of AML w i t h TMDS, were p r e s e n t in 12 patients w i t h CD34 + AML and were not assessable in 10 patients b e c a u s e of an overwhelming blast infiltrate. In eight patients with CD34 +, AML dysplastic features were present o n l y in the erythroid and/or granulocytic series~

In patients w i t h C D 3 4 - AML, m o r p h o l o g i c a b n o r m a l i - ties of the non-blast cell p o p u l a t i o n were m o s t l y confined

Table 1 Clinical features at p r e s e n t a t i o n , FAB subtypes, response to c h e m o t h e r a p y and survival in patients w i t h AML CD34 + and CD34 - a

CD34 + CD34 - Age (yr) 64 (24-81) 63 (14-75) Hemoglobin value (g/d0 8.6 (5-10.5) 9.2 (5.6-13) Leukocyte count ( x 109/L) 8. (1-83) 25. (1-249) Platelet count ( × 109/L) 90. (18-488) 80. (26-240) FAB subtypes b M1 (3), M2 (12) M1 (2), M2 (2) M4 (7), M5 (4), M3 (4), M4 (11) M6 (2), M7 (2) M5 (11) CR (%) 33 73 Survival (too) 2 8

a The results are reported as median value; variation ranges are given in parentheses.

b Number of cases in each FAB category.

Abbreviations:

FAB, French-American-British; AML, acute myeloid leukemia; CR, complete remission rate.

to the granulocytic lineage (seven patients), w h e r e a s my- e l o d y s p l a s i a affecting m o r e t h a n one cell lineage was seen in five patients, none of w h o m fulfilled the cytologic criteria for the diagnosis of AML w i t h TMDS. TMDS was not assessable in 18 patients because of an overwhelming blast infiltrate.

Immunophenotyping:

A l l cases expressed at least one myeloid-associated antigen (CD33, CD13, CD15, CD14, glycopho- rin, and CD41a).

CD34 expression was negatively correlated w i t h the CD14 a n d CD15 positivity, the latter two myelomonocytic antigens having been f o u n d more frequently in C D 3 4 - AML, as r e p o r t e d in Figure 1, w h e r e i m m u n o p h e n o t y p i c data are s u m m a r i z e d .

Unequivocal positivity for the CD41a platelet antigen was found in a m i n o r i t y of cells (5-10%) in six patients w i t h CD34 + AML and in one patient w i t h C D 3 4 - AML.

Inappropriate expression of lymphoid-associated antigens was detected in six patients w i t h CD34 + AML, two of w h o m expressed the CD19 antigen, two the CD10, one the CD2, a n d one the CD7. Positivity for CD7 was found in one patient w i t h C D 3 4 - AML.

Cytogenetic Studies

Results of c h r o m o s o m e investigations are detailed in Tables 2 and 3.

Karyotype at d i a g n o s i s was abnormal in 25/30 patients w i t h CD34 + AML, n i n e of w h o m had MAKA. The most frequent aberrations involved the long arm of c h r o m o s o m e 5. Total or p a r t i a l m o n o s o m y 5q p l u s a d d i t i o n a l aberrations were detected in eight patients w i t h AML-M2, w h e r e a s one patient w i t h AML-M4 had a 5q translocation as the sole aberration. In five cases the abnormal 5q c h r o m o s o m e was found in the context of complex karyotypes.

Other recurring chromosome aberrations in this group of patients were d e l e t i o n s or translocations of 16q22 (four patients), a n d d e l e t i o n s or translocations of 17p and - 7 / 7 q - (three patients). Trisomy 11q, del(11)(q13q23), and m o n o s - omy 17 were f o u n d in two patients each.

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F i g u r e 1 P e r c e n t a g e of A M L c a s e s s h o w i n g m o r e t h a n 20% p o s i t i v i t y for i m m u n o l o g i c m a r k e r s (CD34 + cases: d a r k c o l u m n s ; C D 3 4 - cases: dotted c o l u m n s ) (LM: l y m p h o i d - a s s o c i a t e d markers).

T a b l e 2 C l o n a l c h r o m o s o m e a b e r r a t i o n s i n 2 5 p a t i e n t s w i t h C D 3 4 + A M L P a t i e n t A g e FAB M o d a l A b n o r m a l cells/ n o . (yr) s u b t y p e K a r y o t y p e n o r m a l cells 1 67 M 4 46,XX,der(1)add(1)(q32)i(1) (q10)46,idem,i(11){qlO) 8/3 2 51 M 4 45,XX, - 5,der(22)t(22;?)(q11;?) 6/6 3 61 M 4 47,XY, + 8 5/5 4 54 M2 46,XX,t(5;10)(q12;q26) 8/2 5 33 M6 49,XY, + 11,der(13)t(13;?)(p11;?), + m a r l , + m a r 2 / 9/7 5 0 , i d e m , + m a r 3 6 26 M2 47,XX,t(8;21)(q22;q22),del(15)(q15) 7/3 7 40 M 6 45,XY, - 8,der(13)t(13;?)(q14;?),del(20)(qllq13) 12/5 8 24 M1 46,XY,del(3)(q2 l q 2 6 ) , d u p [ 1 7 ) ( q 1 2 q 1 4 ) 12/4 9 31 M 4 46,XX,t(9;11)(p22;q23) 8/4 10 55 M2 44,XX,del(5)(q13q33),del(16)(q22),der(17) t[17;?)(p12;?), - 18,der(20)t(20;?)(p11;?), - 2 1 / 4 5 , i d e m , + m a r 11 71 M2 46,XX, - 4 , d e l ( 5 ) ( q 2 1 q 3 2 ) , + 1 0 , - 14,del(17)(p11), + m a r 12 47 M 4 47,XX, + 11 13 64 M2 4 6 , X X , d e l ( 6 ) ( q 2 2 ) / 4 7 , i d e m , + 22 14 50 M 4 4 4 , X Y , d e r ( 6 ) t ( 6 ; 7 ) ( p 2 3 ; p 1 4 ) , - 7,der(16)t(11;16) (q13;q22), - 1 9 / 4 5 , i d e m , , m a r l 10/0 15 61 M2 43,XY, - 3, - 5,add(15)(q22), - 17 8/2 16 72 M2 43,XY, - 5,del(11)(q23),t(12;13;15) 10/0 (q13;q13;p11),del(16)(q22),der(17)t(17;?) (p12;?), - 18, - 21 17 69 M2 47,XY, + mar(E-size) 10/0 18 61 M2 45,XY, - 5,i(17q) 7/3 19 69 M5 46,XY,del(11)(q13q23) 8/4 20 73 M7 45,XY, - 17 4/6 21 64 M 7 4 6 , X Y , d e l ( 7 ) ( q 2 2 q 3 5 ) / 4 5 , i d e m , - 9 12/0 22 69 M 4 46,XX,del(16)(q22) 12/6 23 81 M2 46,XX,del(5)(q21q31) 10/0 24 68 M2 44,XX,del(5)(q13q31), - 7,del(11)(q13q23), - 12 6/4 25 70 M1 45,XX, - 21 5/5 10/0 8/3 6/4 10/O

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122 F. Fagioli et al.

Table

3 Clonal c h r o m o s o m e aberrations in 10 patients w i t h C D 3 4 - AML

Patient Age FAB Modal Abnormal cells/

no. (yr) subtypes Karyotype normal cells 1 21 M3 46,XX,t(15;17)(q22;q12) 10/0 2 14 M3 46,XY,t(15;17)(q22;q12),47,idem, + 22 10/0 3 25 M1 45,XY,inv(3)(q21q26), - 8/46,inv(3) 9/2 (q21q26),del(8)(q12) 4 75 M5 46,XY,der[8)t(8;?)(q22;?) 4/6 5 36 M5 46,XX,del(6)(q12q14) 6/4 6 75 M4 47,XY, + 15 8/2 7 68 M4 46,XY,del(5)(q14q21)/43,idem, - X, 9/1 - Y , - 7 8 56 M1 46,XX,del(4)(p15) 7/3 9 60 M4 46,del[6q) 7/3

Nine of 30 patients w i t h CD34 - AML h a d c h r o m o s o m e aberrations, one of w h o m h a d MAKA. In this group, two patients w i t h AML-M3 h a d the t(15;17) and two patients had aberrations of the long arm of c h r o m o s o m e 6. Aberrations involving the long arm of c h r o m o s o m e s 3 a n d 5 were detected in one patient each.

Clinical Features

Clinical data at p r e s e n t a t i o n are s u m m a r i z e d in Table 1. Except for m e d i a n w h i t e b l o o d cell count, no i m p o r t a n t difference e m e r g e d w h e n c o m p a r i n g clinical features in patients w i t h CD34 + AML a n d those w i t h CD34 - AML. The m e d i a n age, h e m o g l o b i n value, and platelet count were simi- lar. The M2 a n d M5 FAB subtypes were m o r e frequently en- c o u n t e r e d in CD34 + a n d C D 3 4 - patients, respectively.

A l l patients were treated w i t h a standard i n d u c t i o n regi- m e n consisting of an a n t h r a c y c l i n e drug w i t h cytarabine, in combination with vindesine, cytarabine and etoposide, w h e n the FAB d i a g n o s i s was M4 or M5. Eight of 30 patients (27%) w i t h CD34 + AML attained c o m p l e t e r e m i s s i o n (CR), com- p a r e d w i t h 22/30 (73%) w i t h CD34 - AML (p = 0.0003). The overall m e d i a n survival was 2 m o n t h s in the CD34 + group a n d 8 m o n t h s in the C D 3 4 - AML.

Cyiogenetic Findings and Clinico-Cytologic Features

In patients w i t h CD34 + AML, two s u b g r o u p s of patients according to the p r e s e n c e or absence of M A K A c o u l d be iden- tified.

A l l n i n e patients w i t h M A K A h a d TMDS (nos. 5, 7, 10, 11, 14, 15, 16, 21, and 24 in Table 2), six of w h o m h a d a mi- nor megakaryoblastic c o m p o n e n t (nos. 5, 10, 11, 14, 16, and 24 in Table 2), as shown by p o s i t i v i t y for the CD41 platelet antigen.

In patients w i t h MIKA or n o r m a l karyotype, TMDS was detected in 3/16 cases, n o n e of w h o m h a d a m i n o r megakaryoblastic c o m p o n e n t .

I n a p p r o p r i a t e e x p r e s s i o n of l y m p h o i d antigens was detected in six patients (nos. 1, 2, 6, 9, 19, a n d 22 in Table 2) w i t h MIKA or n o r m a l karyotype.

A significant difference in the complete r e m i s s i o n rate of these two s u b g r o u p s was detected: n o n e of the patients w i t h M A K A attained a CR, whereas 8/21 [31%) patients (nos.

1, 4, 6, 8, 9, 12, 13, and 25 in Table 2) w i t h MIKA or n o r m a l karyotype attained CR (p = 0.03).

DISCUSSION

M o r p h o l o g i c , i m m u n o l o g i c , and cytogenetic studies have been shown to be valuable in defining disease subsets of AML with distinct clinicopathologic features and prognosis [13-16]. This m u l t i p a r a m e t e r s t u d y of 60 n e w l y d i a g n o s e d AML patients treated at a single i n s t i t u t i o n extends p r e v i o u s ob- servations on CD34 + AML [4-6], showing that a) CD34 + AML has a distinct cytogenetic profile with respect to CD34 - AML; b) w i t h i n CD34 + AML, a subset of patients w i t h distinct cytologic a n d c l i n i c a l features can be r e c o g n i z e d according to the cytogenetic pattern; and c) prognosis in CD34 + AML is worse t h a n in C D 3 4 - AML.

Cytogenetic

Profile of CD34 + AML

The frequent o c c u r r e n c e of aberrations involving the long arm of c h r o m o s o m e 7 in CD34+ AML was r e c o g n i z e d as early as 1988 by Vaughan a n d colleagues [4] and later con- firmed by Borowitz et al. [6], w h o found the - 7 / 7 q - abnor- m a l i t y in 8/26 CD34 + AML as c o m p a r e d w i t h 1/28 CD34 - AML. Likewise, Geller et al. [6] frequently detected abnormalities of c h r o m o s o m e 5 a n d / o r 7 in CD34 + AML. In these series, however, a significant fraction of patients with preced- ing chemotherapy of another t u m o r (secondary AML) or with a prior history of m y e l o d y s p l a s i a was i n c l u d e d .

In this s t u d y of de novo AML, the most frequent chromosome a b n o r m a l i t y in CD34 + patients was - 5 / 5 q - (eight cases), w h e r e a s aberrations of c h r o m o s o m e 7 were detected in three patients. A l l patients w i t h 5q a b n o r m a l i t i e s h a d ad- d i t i o n a l c h r o m o s o m e changes and 5 q - was never found as the sole aberration.

All eight patients w i t h - 5 / 5 q - had features of AML-M2, w h i l e o n l y four patients w i t h CD34 + AML-M2 d i d not show chromosome 5q abnormalities, thus suggesting that the AML- M 2 / - 5 / 5 q - s u b t y p e may r e p r e s e n t a p r e v i o u s l y unrecog- nized cytologic-cytogenetic association among CD34 + AML. Noteworthy is the observation that our patients w i t h AML- M 2 / - 5 / 5 q - showed a p o o r prognosis, n o n e of t h e m having achieved CR w i t h a survival range of less t h a n 1-15 m o n t h s ( m e d i a n 1 month).

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Other r e c u r r i n g c h r o m o s o m e aberrations involved the long arm of c h r o m o s o m e 16 w i t h a b r e a k p o i n t at b a n d q22 a n d the short a r m of c h r o m o s o m e 17 in four a n d t h r e e cases, respectively.

A l l patients w i t h 16q22 aberrations h a d m u l t i p l e chro- m o s o m e changes, frequently trilineage myelodysplasia, and d i d not show a b n o r m a l e o s i n o p h i l s in the BM, suggesting that c o m p l e x karyotypes w i t h aberrations of 16q may be associated w i t h a different cytologic picture, c o m p a r e d w i t h that of patients c a r r y i n g the inv(16)(p13q22). This finding is in k e e p i n g w i t h a p r e v i o u s study showing different clinico- p a t h o l o g i c features in m y e l o i d n e o p l a s i a s w i t h 16q d e l e t i o n versus 16q inversion [17].

A b e r r a t i o n s of the short arm of c h r o m o s o m e 17 have re- c e n t l y b e e n a d d e d to the list of c h r o m o s o m e changes non- r a n d o m l y associated w i t h s e c o n d a r y l e u k e m i a [18], a disease subset in w h i c h the involvement of c h r o m o s o m e s 5 and 7, as well as complex chromosome rearrangements, have been w e l l d o c u m e n t e d .

In t h i s series, aberrations of c h r o m o s o m e 5, 7, 16, a n d 17 o c c u r r e d in the context of c o m p l e x karyotypes in six cases, a n d were detected as single aberrations in two cases only. Thus, s o m e cytogenetic features in CD34 + de novo AML re- call those u s u a l l y f o u n d in secondary AML [18-20]. Notewor- thy is the fact that 25/30 CD34 + patients in this series h a d b e e n p r o f e s s i o n a l l y e x p o s e d to p e s t i c i d e s and organic solvents for m a n y years, w h e r e a s such exposure was u n c o m - m o n (5/30) cases) in C D 3 4 - patients [21].

Other r e c u r r i n g c h r o m o s o m e changes in CD34 + AML, i.e., t r i s o m y 11q a n d del(11)(q13q23), were p r e v i o u s l y de- s c r i b e d in m y e l o d y s p l a s i a a n d p r e l e u k e m i c s y n d r o m e s [22, 23]. M o s t of our CD34 + patients h a d the features of trilineage MDS.

Cytogenetic Patterns and Clinicopathologic Features

Patients w i t h M A K A (i.e., t h r e e or m o r e events of transloca- t i o n or n o n - d i s j u n c t i o n in the s a m e clone) a p p e a r to repre- sent a distinct c l i n i c o p a t h o l o g i c e n t i t y of CD34 + AML, as t h e s e patients frequently showed m y e l o d y p s l a s t i c features of the n o n b l a s t cell p o p u l a t i o n associated w i t h c i r c u l a t i n g megakaryoblasts. S u c h cytologic findings were u n c o m m o n in CD34 + patients w i t h MIKA (one or two aberrant events in t h e a b n o r m a l clone) or w i t h n o r m a l karyotype. A l t h o u g h the r e a s o n a c c o u n t i n g for this difference is u n k n o w n , it is r e a s o n a b l e to a s s u m e that transformation may have involved a n early CD34 + progenitor cell both in patients w i t h M A K A a n d in patients w i t h MIKA or n o r m a l karyotype and that l i m i t e d differentiation along m u l t i l i n e a g e pathways may be m a i n t a i n e d in the former group a n d a b o l i s h e d in the latter. I n a p p r o p r i a t e e x p r e s s i o n of l y m p h o i d - a s s o c i a t e d markers was o n l y detected in CD34 + patients w i t h MIKA or n o r m a l k a r y o t y p e a n d was not detected in patients w i t h M A K A a n d in C D 3 4 - patients.

Clinical Outcome in CD34 + AML

Patients w i t h CD34 + AML are less responsive to chemotherapy t h a n patients w i t h CD34 - AML, r e s u l t i n g in a signifi- cantly lower CR rate and in a shorter overall survival. Notewor- thy, all patients in t h i s s t u d y were treated w i t h the same

i n d u c t i o n regimen, followed by m o n t h l y m a i n t e n a n c e chemotherapy, over a 2-year period.

W h i l e other c l i n i c a l parameters w i t h prognostic predict- ability, s u c h as age a n d WBC count at presentation, c o u l d not account for this discrepancy, patients w i t h CD34 + AML h a d unfavorable cytogenetic a b n o r m a l i t i e s m o r e frequently t h a n patients w i t h CD34 - AML. Furthermore, a particularly severe outcome was obtained in CD34 + patients with MAKA, the presence of w h i c h allowed for the identification of a sub- group of CD34 + AML resistant to i n d u c t i o n therapy. This finding stresses the prognostic importance of karyotype findings in AML.

In c o n c l u s i o n , we have s t u d i e d the cytogenetic and c l i n i c o p a t h o l o g i c features in CD34 + AML, in c o m p a r i s o n w i t h C D 3 4 - AML, s h o w i n g that a distinct cytogentic profile may be associated w i t h CD34 + AML. A m o n g CD34 + AML, a strong a s s o c i a t i o n was f o u n d b e t w e e n the M2 FAB s u b t y p e and c h r o m o s o m e 5q aberrations. Cytogenetic findings in CD34 + AML may be clinically relevant in distinguish- ing CD34 + patients u n l i k e l y to achieve CR w i t h a conven- t i o n a l i n d u c t i o n regimen.

This work was supported by M.U.R.S.T., fondi 40% e 60%, and P.F.- ACRO-CNR- (Rome).

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