1
00:00:00,080 --> 00:00:04,040
Please do it, do it because I 
mean, it changed completely my 

2
00:00:04,040 --> 00:00:05,440
my career. 
And I think it's a great 

3
00:00:05,440 --> 00:00:08,360
opportunity, but not just for 
the funding itself. 

4
00:00:08,360 --> 00:00:12,640
That obviously is, is what we 
need to move forward in our 

5
00:00:12,640 --> 00:00:15,880
career for sure, but also for 
the visibility. 

6
00:00:15,880 --> 00:00:19,000
And because it's, it's, I mean 
the prestigious of these grants 

7
00:00:19,000 --> 00:00:22,280
is very well known in the 
community of hematologist. 

8
00:00:27,360 --> 00:00:30,720
Welcome to EHA Unplugged, the 
official podcast channels of the

9
00:00:30,720 --> 00:00:33,160
European Hematology Association.
EHA. 

10
00:00:33,800 --> 00:00:38,000
I am your host, Isabella Libera,
and today we have the pleasure 

11
00:00:38,000 --> 00:00:40,000
to have with us Doctor Anario 
Machin. 

12
00:00:40,320 --> 00:00:42,640
Welcome. 
Thank you very much for having. 

13
00:00:42,640 --> 00:00:47,120
Me So Doctor Anario Machin is 
HPI at the Hematology 

14
00:00:47,120 --> 00:00:50,600
Experimental Lab, Tonoma de 
Madrid and she's also an 

15
00:00:50,800 --> 00:00:54,800
honorary lecturer at the Center 
for Hemato Oncology at the Barts

16
00:00:54,920 --> 00:00:58,360
Cancer Institute in the Queens 
Mary University of London. 

17
00:00:58,360 --> 00:01:02,240
Her research aims to improve the
understanding and management of 

18
00:01:02,240 --> 00:01:08,320
familial AML acute myeloid 
leukemia and focuses on 

19
00:01:08,320 --> 00:01:12,080
exploring GEM line mutations in 
families with AML. 

20
00:01:12,400 --> 00:01:17,360
Doctor Rheomachin's work has was
supported by an EHA Junior 

21
00:01:17,360 --> 00:01:20,600
research grant. 
Her results have been recently 

22
00:01:20,600 --> 00:01:23,200
published and we will be 
discussing them today. 

23
00:01:23,440 --> 00:01:28,320
So we will start by analyzing 
why she's studying family and 

24
00:01:28,440 --> 00:01:35,280
AML, then why she has focused on
a certain translocation and what

25
00:01:36,680 --> 00:01:40,440
the consequences of this 
translocation are and how they 

26
00:01:41,000 --> 00:01:46,040
activate key leukemia genes. 
And finally, we will see how 

27
00:01:46,040 --> 00:01:48,120
this is clinical relevant at the
moment. 

28
00:01:49,120 --> 00:01:54,960
So let's start by the basis, 
looking at the big picture, why 

29
00:01:54,960 --> 00:02:00,280
work in familial AML? 
Thank you, Mami. 

30
00:02:00,560 --> 00:02:03,920
There are two weeks groups of 
accumulated leukemia the 

31
00:02:03,920 --> 00:02:06,520
sporadic cases, but we are 
always forgetting about the 

32
00:02:06,880 --> 00:02:10,120
familial cases that are the ones
where we are inherited A 

33
00:02:10,360 --> 00:02:12,320
mutation that can cause the 
disease. 

34
00:02:12,640 --> 00:02:15,960
So we this is this was 
recognized very recently by The 

35
00:02:16,080 --> 00:02:19,040
Who classification of myeloid 
neoblasms. 

36
00:02:19,360 --> 00:02:24,360
So before 2015 even if we knew 
that there were some aggregation

37
00:02:24,360 --> 00:02:28,880
in families and nothing was 
really done for the diagnostic 

38
00:02:28,880 --> 00:02:33,640
of these of these families, we 
were investigating in new genes 

39
00:02:33,680 --> 00:02:37,880
that could be like causing this 
predisposition to do acute my 

40
00:02:37,880 --> 00:02:39,840
leukemia and other myeloid 
neoblasms. 

41
00:02:40,160 --> 00:02:43,000
So we considered that it was 
really, really relevant to look 

42
00:02:43,000 --> 00:02:46,840
into these families, identify 
the genetic cause of these of 

43
00:02:46,840 --> 00:02:49,880
these, especially at the point 
of the transplantation. 

44
00:02:49,880 --> 00:02:53,560
Because so far we know that the 
the cure of these patients is 

45
00:02:53,560 --> 00:02:57,320
the, the, the transplantation. 
The best donor is normally a 

46
00:02:57,320 --> 00:03:00,280
familiar or a relative of the of
these patients. 

47
00:03:00,680 --> 00:03:04,600
But if the patient, if the 
relative has also the, the, the 

48
00:03:04,680 --> 00:03:08,560
jetline variant, the the 
recipient will develop the 

49
00:03:08,560 --> 00:03:11,280
disease again. 
So this is what we call donor 

50
00:03:11,280 --> 00:03:14,560
derived leukemia and is really 
aggressive. 

51
00:03:14,880 --> 00:03:17,040
So we need to avoid that. 
So we need to understand the 

52
00:03:17,040 --> 00:03:23,040
genetics behind familial cases. 
Then my work also focus on the 

53
00:03:23,040 --> 00:03:27,520
sporadic disease like so I have 
like a 2 main lines of research 

54
00:03:27,520 --> 00:03:31,400
of my research. 
One focus on familial cases, but

55
00:03:31,400 --> 00:03:34,520
the other is in a sporadic 
disease like for example this 

56
00:03:34,560 --> 00:03:37,560
rare subtype that is the the 
patients with the the 

57
00:03:37,560 --> 00:03:39,640
chromosomal translocation 
between chromosome 6 and 

58
00:03:39,640 --> 00:03:42,840
chromosome 9. 
So this translocation between 

59
00:03:42,840 --> 00:03:46,200
chromosome 6:00 and 9:00, you 
say this is sporadic, it's not. 

60
00:03:46,200 --> 00:03:47,160
Familiar. 
It's not familiar. 

61
00:03:49,120 --> 00:03:50,880
So this creates a fusion 
protein. 

62
00:03:51,320 --> 00:03:53,640
What are the consequences of 
this fusion protein? 

63
00:03:53,640 --> 00:03:56,480
What does it do? 
That was exactly what we wanted 

64
00:03:56,480 --> 00:03:59,680
to to understand with this 
project because it is a 

65
00:03:59,680 --> 00:04:04,120
recognized subtype is again in 
the myeloid classification by 

66
00:04:04,120 --> 00:04:07,640
who? 
But so everybody knows that it 

67
00:04:07,640 --> 00:04:11,840
exists is quite a frequent, but 
the consequences of and the 

68
00:04:11,840 --> 00:04:16,120
function of this fusion gene, it
was still unknown and the basics

69
00:04:16,120 --> 00:04:19,000
didn't have any any specific 
therapy for. 

70
00:04:19,079 --> 00:04:21,600
So what we did know is like 
this. 

71
00:04:21,600 --> 00:04:24,080
The transportation between 
chromosome chromosome 6 and 

72
00:04:24,080 --> 00:04:30,040
chromosome 9 results in a fusion
gene between the DECK gene and 

73
00:04:30,040 --> 00:04:33,720
Nope 214 gene. 
So the consequence of this 

74
00:04:33,720 --> 00:04:38,200
fusion gene is a chimeric 
protein, half of DECK and half 

75
00:04:38,200 --> 00:04:40,960
of Nope 214. 
So that was known. 

76
00:04:41,480 --> 00:04:46,800
But how these kinetic protein 
induces the development of acute

77
00:04:46,800 --> 00:04:48,800
myeloid leukemia was still 
unknown. 

78
00:04:49,240 --> 00:04:52,400
And the patients, these patients
with this translocation have a 

79
00:04:52,400 --> 00:04:54,200
really poor prognosis, 
especially when this 

80
00:04:54,200 --> 00:04:57,640
translocation occur at the same 
time with the fleet three IT DE 

81
00:04:57,640 --> 00:05:01,960
mutation that is quite frequent.
Normally more than 70% of these 

82
00:05:01,960 --> 00:05:05,720
patients also appear these fleet
3 ITD mutation. 

83
00:05:06,040 --> 00:05:08,520
So they the the prognosis of 
these patients is really poor. 

84
00:05:08,560 --> 00:05:12,240
The age of the diagnosis of 
these patients is younger than 

85
00:05:12,240 --> 00:05:15,720
the average for acute malaria 
leukemia or they normally have a

86
00:05:15,760 --> 00:05:18,240
really high rate of relapse so 
that because there is no 

87
00:05:18,240 --> 00:05:21,600
actually so they respond, but 
then they relapse because the 

88
00:05:21,600 --> 00:05:25,040
clone with the translocation is 
still there and it causes the 

89
00:05:25,040 --> 00:05:27,840
relapse of the disease. 
So we really wanted to 

90
00:05:27,840 --> 00:05:32,120
understand how this kinetic 
protein could induce leukemia 

91
00:05:32,440 --> 00:05:35,680
and if there was something that 
we could target to kill these 

92
00:05:35,680 --> 00:05:42,480
leukemic cells. 
So what are the targets of this 

93
00:05:42,480 --> 00:05:47,280
fusion protein? 
So the main finding of our 

94
00:05:47,280 --> 00:05:51,120
project and that we are really 
proud of is like we found that 

95
00:05:51,120 --> 00:05:54,960
BEKNUP 214 acts as a 
transcription factor. 

96
00:05:55,160 --> 00:05:58,800
So it binds to the regulatory 
region of key leukemia genes 

97
00:05:58,800 --> 00:06:04,280
like HOX genes or FOXY one who's
an induced and these induces the

98
00:06:04,280 --> 00:06:06,720
overexpression of these key 
leukemia target genes. 

99
00:06:07,000 --> 00:06:10,080
So then what we know is the 
overexpression of FOXY one or 

100
00:06:10,080 --> 00:06:13,600
HOX genes induces leukemia. 
So this is already known because

101
00:06:13,600 --> 00:06:17,360
they are genes overexpressed in 
other subtypes of leukemia. 

102
00:06:17,680 --> 00:06:21,200
But what we identified was the 
what was causing this 

103
00:06:21,400 --> 00:06:24,560
overexpression, That was the 
binding of Decknum 214 to the 

104
00:06:24,560 --> 00:06:28,600
regulatory regions. 
So then understanding why these 

105
00:06:28,600 --> 00:06:34,120
genes are inducing leukemia, it 
was quite well studied before 

106
00:06:34,720 --> 00:06:37,160
because FOXY one for example, 
blocks differentiation. 

107
00:06:37,160 --> 00:06:42,520
But this is one of the heats 
that normally occur to for to 

108
00:06:42,520 --> 00:06:45,440
induce leukemia leukemia 
development. 

109
00:06:45,840 --> 00:06:48,840
And also as well the over 
expression of hoax genes that 

110
00:06:48,840 --> 00:06:51,600
are really, really well known 
targets and are over expressed 

111
00:06:51,600 --> 00:06:55,680
in other subtitles like the ones
with KMDT to a rearrangements. 

112
00:06:56,560 --> 00:07:00,640
So the the novelty was 
identifying this new this new 

113
00:07:00,640 --> 00:07:03,640
role for techno 214 over 
expressing, inducing the over 

114
00:07:03,640 --> 00:07:06,160
expressing of these teams. 
And what it was more important 

115
00:07:06,200 --> 00:07:12,520
it was the the group 214 in 
binds to this region with the 

116
00:07:12,520 --> 00:07:17,240
help of XPO 1. 
And XPO 1 is a is a protein that

117
00:07:17,240 --> 00:07:21,600
binds to the group 214 and is 
required these binding for the 

118
00:07:21,600 --> 00:07:25,400
over expression of hoax genes 
and FOXY one among other genes. 

119
00:07:27,200 --> 00:07:29,800
And it was really interesting 
because we had a good 

120
00:07:29,880 --> 00:07:34,600
representation of patients with 
A-69 translocation given that it

121
00:07:34,600 --> 00:07:39,040
was a very rare entity. 
And we compare, we compare the 

122
00:07:39,040 --> 00:07:41,080
response of this space of this 
cell, the cells of these 

123
00:07:41,080 --> 00:07:43,840
patients with the T-69 
translocation with the response 

124
00:07:44,240 --> 00:07:49,080
to for other AML subtypes. 
So we treat in all these cells 

125
00:07:49,360 --> 00:07:54,400
with more than 527 compounds. 
And it was really interesting to

126
00:07:54,400 --> 00:07:55,920
find that on the top of the 
list. 

127
00:07:56,200 --> 00:08:00,200
So the the compounds that were 
more specific and more selective

128
00:08:00,600 --> 00:08:03,440
for the T-69 patients were the 
XP-1 inhibitors. 

129
00:08:03,960 --> 00:08:07,320
So there was a clear 
relationship between our 

130
00:08:07,320 --> 00:08:11,360
finding, so identifying XPO one 
being super specific and 

131
00:08:11,360 --> 00:08:16,880
efficient for the T-69 patients 
compared to other AML subtypes 

132
00:08:17,480 --> 00:08:22,200
and the the fact that Techno 214
interacts with XPO 1. 

133
00:08:22,760 --> 00:08:28,520
So then we went a step forward. 
So we found that Techno 214 

134
00:08:28,520 --> 00:08:32,679
requires XPO 1 interaction to 
induce the best person of these 

135
00:08:32,679 --> 00:08:37,159
genes that I mentioned before. 
And when we treat the patient 

136
00:08:37,159 --> 00:08:40,880
cells with XP-1 inhibitors, this
binding is lost. 

137
00:08:41,080 --> 00:08:45,480
And this the expression of these
key leukemia genes was reduced 

138
00:08:45,760 --> 00:08:49,840
causing the the the the kill of 
the of these cells, leukemia 

139
00:08:49,840 --> 00:08:53,040
cells. 
So in a in a way we identify a 

140
00:08:53,040 --> 00:08:57,720
potential targeted therapy 46, 
nine patients so. 

141
00:08:59,040 --> 00:09:02,680
That would be my question. 
Can you use this XPO 1 

142
00:09:02,720 --> 00:09:07,080
inhibitors in patients? 
Is it known whether this is safe

143
00:09:07,240 --> 00:09:09,560
to use and? 
That's, that's a very 

144
00:09:09,560 --> 00:09:13,440
interesting question because 
XP-1 inhibitors 11 cellinexor 

145
00:09:13,440 --> 00:09:16,000
for example, is an XP-1 
inhibitor approved for the 

146
00:09:16,000 --> 00:09:18,800
treatment of multiple myeloma, 
which is great because it's 

147
00:09:18,800 --> 00:09:22,720
approved already. 
So it will speed up the the the 

148
00:09:22,720 --> 00:09:26,240
possibility of use of being used
for acute minor leukemia 

149
00:09:26,240 --> 00:09:31,680
treatment however is very toxic.
So there are new versions of XPO

150
00:09:31,680 --> 00:09:34,520
1 inhibitors coming now and 
being studied in preclinical and

151
00:09:34,520 --> 00:09:38,000
clinical studies. 
So probably in the in the coming

152
00:09:38,000 --> 00:09:42,400
years, we will have more safe 
XPO 1 inhibitors that can be 

153
00:09:42,400 --> 00:09:46,680
definitively be tested. 
So I believe our research will 

154
00:09:47,160 --> 00:09:52,600
pave the way for potential 
preclinical and clinical trials 

155
00:09:53,080 --> 00:09:55,840
for the treatment, in particular
treatment of T-69 patients. 

156
00:09:56,400 --> 00:10:01,640
So does this have any 
implication for other AML 

157
00:10:01,640 --> 00:10:05,040
subtypes? 
That's that's very interesting 

158
00:10:05,040 --> 00:10:06,960
as well. 
And this is actually has been 

159
00:10:06,960 --> 00:10:12,680
studied before because a hoax 
genes are overexpressed in so 

160
00:10:12,680 --> 00:10:17,200
many other subtypes. 
So in those subtypes is being 

161
00:10:17,240 --> 00:10:21,360
the role of XPO one involved in 
the regulation of these genes is

162
00:10:22,000 --> 00:10:25,480
is being currently studying so 
far by other groups. 

163
00:10:25,840 --> 00:10:29,120
So it seems like XPO one by the 
interaction through other 

164
00:10:29,120 --> 00:10:32,240
factors may have a role in the 
upper regulation of these genes 

165
00:10:32,480 --> 00:10:35,720
in other subtypes with these 
things are also up regulated. 

166
00:10:36,200 --> 00:10:42,000
So the the particular use of XPO
1 inhibitors is being currently 

167
00:10:42,480 --> 00:10:44,840
studied for the treatment of 
other patients with the 

168
00:10:44,840 --> 00:10:50,480
respiration of XPO 1 of HOX 
genes like for example MPN 1 

169
00:10:50,480 --> 00:10:54,320
motivated patients or MLLA 
rearranged patients as well. 

170
00:10:55,040 --> 00:10:56,680
So what are the next steps for 
this? 

171
00:10:56,680 --> 00:10:58,680
Research. 
So definitely we need to expand 

172
00:10:58,720 --> 00:11:03,480
these research in other models 
before starting a clinical trial

173
00:11:03,920 --> 00:11:07,200
and but there are still lots of 
questions from the molecular 

174
00:11:07,200 --> 00:11:11,600
perspective that are still open.
So I really want to understand 

175
00:11:11,840 --> 00:11:15,800
how these two proteins interact 
through which domains. 

176
00:11:16,160 --> 00:11:21,800
And if apart from the genes that
we looked into like Hoxins or 

177
00:11:21,800 --> 00:11:25,400
Foxy one, as I mentioned before,
if there are other key leukemia 

178
00:11:25,400 --> 00:11:28,600
genes that are also regulated by
the interaction of these two 

179
00:11:28,600 --> 00:11:32,160
proteins, the kinetic protein 
and XPO one that may have a role

180
00:11:32,200 --> 00:11:36,320
in leukemia even if they've not 
been related to a metopoiesis or

181
00:11:36,320 --> 00:11:39,520
leukemia before. 
To identify other mechanisms 

182
00:11:39,960 --> 00:11:44,480
that that can can explain this 
malignant transformation and how

183
00:11:44,480 --> 00:11:47,720
this subtype is is very 
aggressive as well as the 

184
00:11:47,720 --> 00:11:50,320
interaction with free 3 ITD 
mutation. 

185
00:11:50,680 --> 00:11:53,960
Because it's quite interesting 
that these patients with the D69

186
00:11:53,960 --> 00:11:58,280
translocation also acquired the 
Fleet 3 ATD mutation in more 

187
00:11:58,280 --> 00:12:01,080
than 70% of the cases. 
So it will be very interesting 

188
00:12:01,080 --> 00:12:05,320
to see if there is any 
relationship between the fusion 

189
00:12:05,320 --> 00:12:09,280
protein Fleet 3 ATD. 
So if they if they have a role 

190
00:12:09,360 --> 00:12:14,400
in inside cells and if X PO1 is 
somehow involved in this. 

191
00:12:14,720 --> 00:12:18,040
So because if that's the case, 
if X PO1 is somehow related with

192
00:12:18,040 --> 00:12:22,520
Fleet 3 ATD, then we kind of 
expand the use of XP-1 

193
00:12:22,520 --> 00:12:26,160
inhibitors for other sometimes 
like flea 380 mutated patients, 

194
00:12:26,160 --> 00:12:31,320
which are really, really common.
So this project was funded 

195
00:12:31,440 --> 00:12:38,280
thanks to a grant from EHA. 
Can you reflect on how this 

196
00:12:38,480 --> 00:12:42,440
grant has helped your career? 
Yeah, I mean, I'm really, really

197
00:12:42,440 --> 00:12:45,640
grateful to the EHA because I 
think really this, this getting 

198
00:12:45,640 --> 00:12:50,920
this grant was key turning point
on, on my, on my career. 

199
00:12:51,200 --> 00:12:53,480
So it helped me so much to my 
independence. 

200
00:12:53,800 --> 00:12:57,720
It I, I was, I was appointed as 
a Lecter when I got this, this 

201
00:12:57,720 --> 00:13:02,240
fellowship because it was my 
first funding as a, as API. 

202
00:13:02,640 --> 00:13:05,960
So then I could establish my own
research group at the Bar's 

203
00:13:05,960 --> 00:13:09,600
Cancer Institute in London. 
And after that I got more 

204
00:13:09,600 --> 00:13:12,640
funding and I gave me the 
opportunity also to complete 

205
00:13:12,840 --> 00:13:16,120
this super exciting project that
we recently published. 

206
00:13:16,120 --> 00:13:18,320
So it was a really beautiful 
story. 

207
00:13:18,760 --> 00:13:23,720
Now I moved my group to, to 
Madrid today, but keeping my, my

208
00:13:24,480 --> 00:13:27,760
relationship with, with London. 
So, but everything I started 

209
00:13:27,760 --> 00:13:31,520
with the EHA research grant. 
So I'm really, really grateful. 

210
00:13:33,440 --> 00:13:37,120
So what would you tell young 
investigators that they're 

211
00:13:37,120 --> 00:13:40,480
thinking of applying for a Young
EHA grant? 

212
00:13:41,000 --> 00:13:44,160
Please do it. 
Do it because I mean it changed 

213
00:13:44,160 --> 00:13:47,120
completely my my career and I 
think it's a great opportunity, 

214
00:13:47,360 --> 00:13:51,720
but not just for the funding 
itself that obviously is is what

215
00:13:51,720 --> 00:13:56,080
we need to move forward in our 
career for sure, but also for 

216
00:13:56,080 --> 00:13:57,960
the visibility. 
And there because it's it's the 

217
00:13:57,960 --> 00:14:01,880
prestigious of these grants is 
very well known in the community

218
00:14:01,880 --> 00:14:05,240
of hematologists and researchers
in hematology. 

219
00:14:05,480 --> 00:14:09,480
So that's one of the key things 
as well because it gives you 

220
00:14:09,480 --> 00:14:12,760
visibility. 
So then you get much more 

221
00:14:13,080 --> 00:14:16,320
opportunities around like 
tearing sessions, being 

222
00:14:16,320 --> 00:14:20,280
involved, giving talks and 
knowing all the scientists or 

223
00:14:20,280 --> 00:14:22,880
their hematologist. 
So it's like a fantastic 

224
00:14:22,880 --> 00:14:25,360
opportunity. 
So please do it there. 

225
00:14:25,520 --> 00:14:28,280
It's not only the the junior one
that is the one that I got, but 

226
00:14:28,280 --> 00:14:32,160
there is there are more like the
advanced and also lots of 

227
00:14:32,160 --> 00:14:36,360
opportunities for collaboration 
with among different groups. 

228
00:14:38,160 --> 00:14:40,480
Are you involved in other ways 
in AK now? 

229
00:14:41,040 --> 00:14:43,960
Yeah, I'm part of the mentoring 
program committee. 

230
00:14:44,320 --> 00:14:48,720
So he's a new program that is 
launching EATA this year. 

231
00:14:49,120 --> 00:14:54,440
So he's we are matching mentees 
and mentors and I hope it's 

232
00:14:54,440 --> 00:14:56,960
going to work right. 
Yeah, I'm, I'm part of this this

233
00:14:56,960 --> 00:15:01,280
committee organizing, organizing
this new initiative that I think

234
00:15:01,280 --> 00:15:04,680
is going to be fantastic and 
hopefully it will continue for 

235
00:15:04,680 --> 00:15:08,360
many years. 
What is the best part of your 

236
00:15:08,360 --> 00:15:14,080
job? 
Well, but definitely like 

237
00:15:14,480 --> 00:15:18,760
knowing people doing research in
in hematology. 

238
00:15:18,760 --> 00:15:22,360
So I think it's the part that I 
love the most, like seeing what 

239
00:15:22,360 --> 00:15:26,520
others do and collaborating 
with, with other people, with 

240
00:15:26,520 --> 00:15:30,720
the, with the prejudice was 
funded by, by, I'd say I had the

241
00:15:30,720 --> 00:15:34,160
opportunity of supervising for 
the first time my own PhD as 

242
00:15:34,160 --> 00:15:40,040
student and seen how happy she 
was when, when the experiments 

243
00:15:40,040 --> 00:15:43,760
worked, when our hypothesis, the
one that I wrote when I applied 

244
00:15:43,760 --> 00:15:48,200
for the EITA worked as well. 
And it was guiding the, the 

245
00:15:48,200 --> 00:15:51,920
continuation of the project. 
I think it was the most 

246
00:15:51,920 --> 00:15:54,800
rewarding thing that I ever, 
ever experienced. 

247
00:15:55,160 --> 00:15:58,600
So that confirmed that I what I 
want to do, like research, 

248
00:15:58,880 --> 00:16:02,440
training other people, like 
building my group and and see 

249
00:16:02,440 --> 00:16:04,840
how working together we can get 
somewhere. 

250
00:16:06,560 --> 00:16:08,480
And what is more difficult in 
your job? 

251
00:16:08,960 --> 00:16:10,680
In funding. 
Getting the fun. 

252
00:16:11,440 --> 00:16:13,960
So, yeah, yeah, definitely 
that's that's the most 

253
00:16:13,960 --> 00:16:17,280
challenging part for for every 
research. 

254
00:16:17,360 --> 00:16:19,600
I mean the future is in the 
collaborations, that's for sure.

255
00:16:19,600 --> 00:16:23,640
So I think we can't be experts 
of everything. 

256
00:16:24,040 --> 00:16:28,840
So if we want to make research 
that change the way in which we 

257
00:16:28,840 --> 00:16:34,160
treat the patients, the way in 
which the patients are cured and

258
00:16:34,200 --> 00:16:38,680
managed, we definitely need to 
work together with including 

259
00:16:39,320 --> 00:16:41,680
everything. 
No, like artificial intelligence

260
00:16:41,680 --> 00:16:47,280
now by informaticians research 
and doing experiments hand on in

261
00:16:47,280 --> 00:16:51,160
the lab and lots of people 
thinking, connecting and 

262
00:16:51,800 --> 00:16:54,200
talking, talking and doing 
brainstorming. 

263
00:16:54,560 --> 00:16:56,840
So that's, that's the future. 
So I think the funding will come

264
00:16:56,840 --> 00:16:59,600
through all these ways as well 
that most of the founder bodies 

265
00:16:59,600 --> 00:17:03,560
are also seen that that's the 
the way in which we should be 

266
00:17:03,560 --> 00:17:05,680
working. 
Yeah. 

267
00:17:06,400 --> 00:17:09,160
For clinical trials or for 
anything that you have to test 

268
00:17:09,160 --> 00:17:11,680
now. 
So you will need a lot of. 

269
00:17:11,800 --> 00:17:13,400
Totally. 
Yeah, collaboration and 

270
00:17:13,400 --> 00:17:15,640
interactions. 
Exactly with industry as well. 

271
00:17:15,640 --> 00:17:19,800
So definitely that's the future.
We can't forget the rare 

272
00:17:19,800 --> 00:17:21,520
subtypes of acute malial 
leukemia. 

273
00:17:21,640 --> 00:17:24,160
So because they, it matters, 
it's a really aggressive 

274
00:17:24,200 --> 00:17:28,680
disease, but there are some 
subtypes within the, the AML 

275
00:17:28,680 --> 00:17:33,720
that are even worse than others.
And they, we, we, we can't 

276
00:17:33,720 --> 00:17:36,000
forget those. 
Because I was asked in lots of 

277
00:17:36,000 --> 00:17:39,760
interviews why focusing on a 
rare subtype within a rare 

278
00:17:39,760 --> 00:17:42,720
disease? 
Because I mean, fortunately, AML

279
00:17:42,720 --> 00:17:45,960
is not really, really frequent, 
but it's super aggressive. 

280
00:17:46,000 --> 00:17:49,520
Let's focus on restart types as 
well because they matter. 

281
00:17:49,520 --> 00:17:52,680
They are, they are patients, 
they, it's people behind 

282
00:17:52,840 --> 00:17:56,160
suffering of this disease. 
So that's one thing that 

283
00:17:56,160 --> 00:18:00,560
collaborations are needed for 
make a science bigger and to get

284
00:18:01,120 --> 00:18:05,520
impactful results, and that's 
it. 

285
00:18:06,920 --> 00:18:11,160
Well, thank you very much for 
being with us today, Doctor Leo 

286
00:18:11,160 --> 00:18:15,280
Machine, and thank you for all 
the audience to report listening

287
00:18:15,360 --> 00:18:17,520
and stay tuned for more 
episodes. 

288
00:18:18,000 --> 00:18:19,480
Thank you very much for the 
mutation.